bromochloroacetic-acid and Arthritis--Rheumatoid

Anti-keratin antibody (AKA) is a serum antibody for patients with rheumatoid arthritis (RA), and it has a high specificity. Diagnostic role of AKA in RA was evaluated in this study.. PubMed, EMBASE, and Web of Science were searched to acquire eligible studies. Articles published before 15 March 2018 were considered to be included. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the risk of bias and application concern of the included articles. Pooled analysis of diagnostic indicators of AKA for RA was conducted by using a random effects model. Subgroup analysis was employed to explore the potential influencing factors. RevMan 5.3, Stata 11.0, and Meta-DiSc 1.4 software were used in this study.. A total of 15 studies (2350 positive and 2067 negative participants) were included. The pooled sensitivity was 0.46 (95% CI 0.44-0.48), pooled specificity was 0.94 (95% CI 0.93-0.95), and pooled diagnostic odds ratio was 15.86 (95% CI 9.48-26.52). In addition, the area under the curve was 0.7194.. The current evidence indicated that AKA has high diagnostic specificity in RA and may be useful for RA diagnostic application in clinic.

Topics: Arthritis, Rheumatoid; Autoantibodies; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Sensitivity and Specificity

Rheumatoid factor and antibodies against cyclic citrullinated peptides represent a diagnostic hallmark in rheumatoid arthritis (RA). However, over the last decades many other autoantibodies have been identified. Several proteins can trigger an aberrant autoimmune response in their native form while others acquire this feature after post-translational modifications such as citrullination, carbamylation or acetylation. It is of interest that also the enzymes catalyzing such post-translational modifications (e.g. the protein arginine deiminases) can transform themselves into autoantibodies in RA. The purpose of this review article is to provide an overview of relevant literature published over the last years regarding novel autoantibodies and their possible diagnostic and prognostic significance in RA.

Topics: Antibodies, Antinuclear; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Citrullination; Epstein-Barr Virus Nuclear Antigens; Humans; Hydrolases; Keratins; Peptide Fragments; Peptides, Cyclic; Protein Carbamylation; Rheumatoid Factor; Vimentin; Viral Proteins

Topics: Acute-Phase Proteins; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Calcium-Binding Proteins; Disease Progression; Filaggrin Proteins; Humans; Interleukin-1; Intermediate Filament Proteins; Keratins; Matrix Metalloproteinase 3; Peptides, Cyclic; Predictive Value of Tests; Prognosis

The overview provides the knowledge about rheumatoid factor isotypes and their significance in the case of rheumatoid arthritis. New immunological methods have been introduced in the last decade proving their validity in seronegative rheumatoid arthritis. Antikeratin and anticitrulline antibodies were found to be useful diagnostic tools for seronegative and early rheumatoid arthritis. The methods perform well for scientific needs as well as in daily clinical practice.

Topics: Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Citrulline; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Keratins; Prognosis; Rheumatoid Factor; Time Factors

AN IMPORTANT CLINICAL TOOL: A sensitive and specific marker allowing the diagnosis of rheumatoid arthritis, and even more importantly an early assessment of severity, would be a highly valuable clinical tool. Autoantibodies have been found to be quite useful in clinical practice for diagnosis and assessing prognosis. EARLY-STAGE RHEUMATOID ARTHRITIS: Ideally, the marker should be sensitive and specific when the first signs of the disease develop. To date, only the rheumatoid factor and anti-filaggrin antibodies (including anti-stratum comeum or "anti-keratin" and anti-perinuclear factors) have been used with sufficiently acceptable standards. IgM rheumatoid factors can be detected in about 80% of patients with rheumatoid arthritis but they lack specificity since they are also found in other auto-immune conditions (lupus, Sjögren's syndrome), in chronic infections, and in certain lymphoproliferative syndromes (with or without cryoglobulinemia). Anti-filaggrin antibodies are more specific (70 to 100% depending on the study) but can only be detected in 30 to 50% of the patients. High titers of rheumatoid factors (IgM and/or IgA) and anti-filiggrin antibodies are factors of poor prognosis because they are associated with destructive polyarthritis, sometimes complicated with extra-articular signs (nodules, vasculitis). Among the new autoantibodies being studied, only anti-Sa appears to have real diagnostic and prognostic value. The recent data must be confirmed. STRATEGIES FOR OVERT DISEASE: Systematic and repeated assay of autoantibody levels is not warranted in patients with overt disease. Anti-Ro-SS/A, ANCA can however, in some cases, detect unusual complications. THREE STRATEGIES WOULD BE PARTICULARLY INTERESTING: The first is to search for highly specific markers with the aim of identifying a subgroup of rheumatoid arthritis patients as early as possible who have specifically defined clinical, biological and disease-progression criteria. The second is to validate composite scores integrating autoantibodies to achieve early definition of disease severity. The third is to search for markers of progression, particularly autoantibodies, that could modulate inflammatory processes and osteo-cartilaginous degeneration.

Topics: Antibodies, Antineutrophil Cytoplasmic; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Enzyme-Linked Immunosorbent Assay; Epidermis; Filaggrin Proteins; Fluorescent Antibody Technique; Humans; Immunoglobulin M; Intermediate Filament Proteins; Keratins; Peroxidase; Prognosis; Rheumatoid Factor; Ribonucleoproteins; Sensitivity and Specificity

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Biomarkers; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratins; Sensitivity and Specificity

Topics: Antibodies, Antineutrophil Cytoplasmic; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Carrier Proteins; Centrosome; DNA-Binding Proteins; Filaggrin Proteins; Heat-Shock Proteins; Humans; Intermediate Filament Proteins; Keratins; Tacrolimus Binding Proteins

Cytokeratins are a major constituent of the cytoskeleton in eukaryotic cells and are vital for the maintenance of cell structure and function. Identification of increased levels of IgA antibodies to these intracellular structures has prompted increasing interest in the potential role between the gut and the immune system in the pathogenesis of inflammatory arthritis. This review examines the salient features of cytokeratin (CK) antibodies that are relevant to inflammatory arthropathies and discusses the meaning and potential applications of these findings in the context of the different arthropathies.. Review of the literature on antibodies to cytokeratins in inflammatory arthropathies, using MEDLINE and the key words (cyto)keratin and arthritis. The studies were interpreted and critiqued.. Increased levels of IgA antibodies to CK-18 and epidermal keratins have been shown by enzyme-linked immunosorbent assay (ELISA) in rheumatoid arthritis and psoriatic arthritis. Levels were not increased in osteoarthritis or reactive arthritis.. CK-18 is present within endothelial cells lining synovial blood vessels in patients with various rheumatic conditions, including rheumatoid arthritis, as well as in normal controls. Damage to synovial endothelial cells may lead to increased production of antibodies to CK-18. The CK antibody response is independent of the polyclonal immunoglobulin expansion typical of RA and is not specific for RA because an increased IgA response to CK-18 also has been shown in psoriasis and in psoriatic arthritis. Damage to synovial endothelial cells does not explain the increased autoantibody production in other conditions such as psoriasis. In this condition, damage to epithelial tissues in other regions of the body (e.g, skin, gut, kidney) may lead to production of keratin antibodies that recognize epitopes common to all CK, including CK-18. The reason for an elevated IgA anti-CK response rather than an IgG or IgM response is not clear. It cannot be explained by a general increase in serum IgA levels. Most of the conditions in which raised levels of these antibodies were found have been associated to different degrees with abnormalities of the gut mucosa or mucosal immune system. It appears that the nature of autoantibodies to CK-18 is probably natural rather than pathogenic. Currently there are no data on the source of the IgA antibodies to cytokeratins (i.e., mucosal or central immune system). Indeed, it may depend on the disease.

Topics: Arthritis, Rheumatoid; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin A; Keratins; Male

Antiperinuclear factor (APF) and antikeratin antibody (AKA) have long been known to be associated with rheumatoid arthritis. Human buccal mucosa epithelial cells have hitherto been required as the substrate in the APF test, while AKAs are detected on rat esophagus sections, using an indirect immunofluorescence technique. These two autoantibodies proved to be interrelated. Cytoplasmic inclusions in buccal cells have presumptively been termed keratohyalin granules and the APF target antigen colocalizes exactly with that of antiprofilaggrin antibody within the perinuclear organelles. The latter protein has convincingly been identified as the genuine specificity of the so-called AKA.

Topics: Animals; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Epitopes; Filaggrin Proteins; Humans; Immunoblotting; Inclusion Bodies; Intermediate Filament Proteins; Keratins

Rheumatoid arthritis (RA) is associated with several autoantibodies specific enough to serve as diagnostic and prognostic markers. These include rheumatoid factor (RF), antikeratin antibody (AKA), antiperinuclear factor (APF), and anti-RA33. The first three, and possibly also anti-RA33, may precede the onset of clinical RA. The prevalence of positive test reactions depends on the period between taking the specimen and onset of disease; when the period is short, the prevalence is nearly the same as in established disease. Thus, RA has a long asymptomatic period with broadening immunological activity. The assays for AKA and APF (and possibly also for anti-RA33), compared with RF testing, yielded greater specificity rather than the ability to define any subgroup with particularly severe disease. Used together, the above marker antibodies may form a new and more enlightened basis for defining seropositive RA. It is commonly believed that genetically mediated immune response plays an important role in the initiation of RA. However, the role of the major histocompatibility complex antigens may be in modulation of the inflammatory reaction in a later phase.

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Fluorescent Antibody Technique; Humans; Keratins; Prognosis; Rheumatoid Factor

On the basis of the literature and the author's own investigations the present knowledge about antikeratin antibodies (AKA) in rheumatoid arthritis (RA) is summarized. The specificity of AKA for RA is described between 90% and 100%, but the sensitivity is reported as varying from 36% to 80%. In conclusion, AKA have great diagnostic value in RA and, high titre AKA, were found to be pathognomonic for RA. Further studies are necessary to confirm if AKA are also of prognostic and pathogenetic value in RA.

Topics: Antibodies; Arthritis, Rheumatoid; Fluorescent Antibody Technique; Humans; Keratins; Prognosis

Topics: Antibodies; Arthritis, Rheumatoid; Chronic Disease; Humans; Intermediate Filament Proteins; Keratins; Lupus Erythematosus, Systemic; Rheumatic Diseases; Scleroderma, Systemic; Sjogren's Syndrome; Spondylitis, Ankylosing; Vimentin

To determine whether measurements of different autoantibodies (Ab) and cytokines are useful to distinguish very early rheumatoid arthritis (RA) from other inflammatory rheumatisms.. From a population-based recruitment, 32 patients with very early polyarthritis (median duration: 4 months) were studied. Evaluations at entry (M0), and at 6 (M6) and 12 months (M12). Ab tested: rheumatoid factors (RF) by agglutination methods and ELISA, antiperinuclear factor (APF), antikeratin Ab (AKA), anti-Sa and antinuclear Ab. Cytokine production (TNFalpha, IL2, IFNgamma, IL1beta, IL10) in whole blood cell culture (WBCC) was determined at M0. At M12, patients were classified as having RA (N = 15) or other rheumatic diseases.. At M0, AKA/APF and anti-Sa Ab frequencies were low, 13% and 7%, respectively. While most Ab detected at M0 persisted, others appeared during follow-up, particularly APF, which rose from 13 to 40% at M12. At M6, IgM-RF was detected in two RA patients exclusively by ELISA. AKA/APF were found to be highly specific markers for RA (100% specificity). At some time during follow-up, two RF-negative RA patients were AKA-positive. In two patients, AKA and APF were present at M0 before they satisfied ACR criteria. IL2 and IFNgamma production was significantly lower (P < 0.05) for RA patients.. AKA/APF and anti-Sa Ab were detected in community cases of very early RA. AKA/APF and RF detected by ELISA might contribute to an earlier diagnosis of RA. Low production of IFNgamma and IL2 in WBCC constituted a distinct immunopathological feature in very early RA patients.

Topics: Antibodies, Antinuclear; Antibody Specificity; Arthritis, Rheumatoid; Biomarkers; Cells, Cultured; Diagnosis, Differential; Filaggrin Proteins; Follow-Up Studies; Humans; Interferon-gamma; Interleukin-10; Interleukin-2; Intermediate Filament Proteins; Keratins; Leukocytes, Mononuclear; Longitudinal Studies; Pilot Projects; Prospective Studies; Rheumatoid Factor; Tumor Necrosis Factor-alpha

Antiperinuclear factor (APF), "antikeratin antibodies" ("AKA"), and antibodies to human epidermis filaggrin (AFA), are highly specific serological markers of rheumatoid arthritis (RA), which recognise epitopes on various isoforms of (pro)filaggrin. It was proposed that these antibodies are globally named antifilaggrin autoantibodies. Here the diagnostic value of the detection of each one is compared and the overlap between the three tests evaluated.. 492 serum samples were tested, including 279 RA serum samples, taken from patients in France and Belgium. APF and "AKA" titres were estimated by indirect immunofluorescence, and AFA titres by immunoblotting on filaggrin enriched human epidermis extracts.. By a convenient choice of the positivity thresholds, the diagnostic sensitivity and specificity of the tests were shown to be similar (0.52 and 0.97, respectively). Although the antibody titres were strongly correlated, the associations APF-AFA or AFA-"AKA" permitted more than 52% or 55% of RA to be diagnosed, with a specificity of 0.99.. APF, "AKA", and AFA detection have a similar diagnostic value. However, because the three tests do not totally overlap, associating APF with "AKA" or AFA with "AKA" can improve diagnostic sensitivity. None of the three antigens used bear all the epitopes recognised by antifilaggrin autoantibodies.

Topics: Adolescent; Adult; Aged; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Epidermis; Female; Filaggrin Proteins; Fluorescent Antibody Technique, Indirect; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Sensitivity and Specificity

Aurokeratinate (Auro-Detoxin) was administered intramuscularly to patients with chronic rheumatoid arthritis, using two different dosage schedules and measuring serum gold concentration. (1) Using slowly rising doses (as generally practised) the gold level gradually rose to 3.2 microgram/ml after four weeks (before the ninth injection), without reaching cumulation equilibrium. Elimination from serum occurred during this phase, with a half-life of 3-5 days. When treatment was continued at about 25 mg gold twice weekly, the cumulation equilibrium was reached with a minimal value at 3.5 microgram/ml and a maximal one of 6 microgram/ml, elimination half-life then being increased to nine days. During the subsequent maintenance treatment with 65 mg gold once a month the serum-gold concentration fell to about 1 microgram/ml, maximal values being about 6 microgram/ml, with an elimination half-life of 11 days. (2) With a constant dose of about 25 mg gold twice weekly, cumulation equilibrium was reached after two weeks (3.4 microgram/ml before the fifth injection), while on 50 mg gold every 14 days as maintenance dose the serum concentration was between 2 microgram/ml minimally and 6 microgram/ml maximally. At the modified dosage the drug was well tolerated.

Topics: Arthritis, Rheumatoid; Gold; Gold Alloys; Half-Life; Humans; Keratins; Kinetics

BACKGROUND There have been few studies on the value of various antibody combinations in rheumatoid arthritis (RA) diagnosis, and a lack of studies with large sample sizes, especially in the Chinese population. This study retrospectively evaluated the diagnostic value of a combined assay of five auto-antibodies [anti-cyclic citrullinated peptide (anti-CCP), anti-keratin (AKA), anti-RA 33, glucose-6-phosphate isomerase (GPI), and rheumatoid factor (RF)] for RA. MATERIAL AND METHODS Data were obtained from 5,725 patients with rheumatic diseases in Southwest Hospital of Chongqing from 2011 to 2014. Detection of the five serological markers was performed for all study patients using the appropriate method for each antibody. RESULTS It was found that of the 5,725 patients, the positive rates for RF, anti-CCP, anti-RA 33, AKA, and GPI were 52.5%, 40.1%, 12.8%, 12.0%, and 50.0% respectively. In RA patients, the positive rates were 83.3%, 68.5%, 16.6%, 20.8%, and 77.9% respectively, which were all significantly higher than those detected in patients with the other diseases (p<0.01). The areas under the receiver operator characteristic (ROC) curve for RF, anti-CCP, anti-RA 33, AKA, and GPI were 0.857, 0.831, 0.528, 0.602, and 0.822 respectively, indicating that these five serological markers display favorable diagnostic value for RA. There were positive correlations between anti-CCP antibody and RF and GPI (p<0.01) and between RF and GPI (p<0.01), but no correlation between anti-RA 33 and AKA (p<0.01). The specificity of the combination of anti-CCP, AKA, and GPI was 100% for RA diagnosis. CONCLUSIONS The combined assay of serological markers significantly improved the diagnostic specificity for RA. The diagnostic value of RF for RA was the highest and the combined assay for anti-CCP, AKA, and GPI had the highest specificity for RA diagnosis.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Child; China; Female; Glucose-6-Phosphate Isomerase; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic; Retrospective Studies; Rheumatoid Factor; ROC Curve; Sensitivity and Specificity

The study aimed to determine the serum level of glucocorticoid-induced tumor necrosis factor receptor family-related protein ligand (GITRL) in patients with rheumatoid arthritis (RA) and investigate its clinical significance. GITRL levels were measured by enzyme-linked immunosorbent assay (ELISA) in 88 RA patients, 20 osteoarthritis (OA) patients, and 20 healthy controls (HCs). Anti-cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor immunoglobulin G (RF-IgG) were also tested by ELISA. RF-IgM, anti-keratin antibody (AKA), and anti-perinuclear factor (APF) antibodies and the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulins were measured by standard laboratory techniques. The disease activity was evaluated by the 28-joint count Disease Activity Score (DAS28). GITRL concentrations were significantly elevated in both serum and synovial fluid (SF) of RA patients. GITRL levels in RA sera were significantly higher than those in matched SFs. Positive correlations were found between serum GITRL levels and inflammation parameters or autoantibody production. GITRL levels are significantly elevated in RA serum and SF and are positively correlated with autoantibody production in RA, suggesting a role of GITRL in the development of RA.

Topics: Aged; Arthritis, Rheumatoid; Autoantibodies; C-Reactive Protein; Female; Humans; Keratins; Male; Middle Aged; Osteoarthritis; Peptides, Cyclic; Synovial Fluid; Tumor Necrosis Factors

Retrospective study to evaluate the diagnostic utility of rheumatoid factor (RF), anticyclic citrullinated peptide antibodies (ACPA) and antikeratin antibodies (AKA) in a broad age range of patients with rheumatoid arthritis (RA).. Clinical and serological data from patients with RA were collected and analysed. Patients were stratified according to age (<16 years [juvenile idiopathic arthritis; JIA], 16-40 years; 41-60 years and >60 years) and sex.. The study included 3725 patients. There were no significant sex-related differences in rates of RF, ACPA or AKA positivity. RF, ACPA and AKA positivity were significantly less common in patients aged <16 years than those aged ≥ 16 years. There were no other significant differences between age groups.. RF, ACPA and AKA have better diagnostic value for RA in adult patients than in patients with JIA. A combination of RF, ACPA and AKA serological testing may be a useful diagnostic tool for RA in Chinese adults.

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Asian People; Autoantibodies; Biomarkers; Child; Child, Preschool; Female; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic; Retrospective Studies; Rheumatoid Factor

To systematically evaluate the values of 4 serum markers in the diagnosis of rheumatoid arthritis (RA).. Serum samples were obtained from 278 RA patients and 510 control subjects and the levels of rheumatoid factor (RF), anticyclic citrullinated peptide antibody (CCP), antikeratin antibody (AKA), and glucose-6-phosphate isomerase (GPI) were detected using immune turbidimetry, ELISA, indirect immunofluorescence, and ELISA, respectively. The values of these 4 serum markers and their combinations in RA diagnosis were systemically assessed.. In RA diagnosis using one serum marker, two markers, and three or four markers, RF, RF+CCP, RF+CCP+GPI, respectively, had the highest sensitivity; CCP, CCP+AKA, and RF+CCP+AKA+GPI, respectively, had the highest specificity; CCP, CCP+GPI, and RF+CCP+AKA+GPI, respectively, had the highest positive predictive value; GPI, RF+CCP, and RF+CCP+GPI, respectively, had the highest negative predictive value; CCP, CCP+GPI, and RF+CCP+AKA+GPI, respectively, had the highest positive likely ratio; GPI, RF+CCP, and RF+CCP+GPI, respectively, had the lowest negative likely ratio.. CCP, RF+CCP, and RF+CCP+GPI are the most ideal for RA diagnosis using one, two, and three or more markers, respectively. CCP is the essential marker for RA diagnosis, and a combined detection of the serum makers can significantly improve the diagnostic accuracy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Case-Control Studies; Citrulline; Female; Glucose-6-Phosphate Isomerase; Humans; Keratins; Male; Middle Aged; Rheumatoid Factor; Young Adult

To evaluate the diagnostic value of anti-mutated citrullinated vimentin antibodies (anti-MCV), anti-cyclic citrullinated peptides antibodies (anti-CCP), anti-glucose-6-phosphate isomerase antibodies (anti-GPI) and anti-keratin antibodies (AKA) and rheumatoid factor (RF) in rheumatoid arthritis (RA).. The five auto-antibodies were detected in serum samples of 56 patients with RA, 21 patients with systemic lupus erythematosus (SLE), 11 with ankylosing spondylitis (AS), six with Sjögren's syndrome (SS), four with connective tissue disease (CTD) and 20 healthy controls. Anti-MCV, anti-CCP and anti-GPI were detected by enzyme-linked immunosorbent assays (ELISA), AKA was determined by indirect immunofluorescence and RF was determined by rate nephelometry.. In RA, anti-MCV and anti-GPI had the highest sensitivity (78.6% and 75.0%, respectively), anti-CCP and AKA had the highest specificity (97.6%). Anti-GPI had the lowest specificity (64.3%), and AKA had the lowest sensitivity (48.2%). When two antibodies were detected together, the sensitivity of anti-MCV/anti-CCP/RF were highest (92.9%) with a lower specificity (73.8%). The combination of anti-MCV/anti-CCP had a slightly decreased sensitivity (89.3%) and the same specificity (73.8%).. The combination RF/anti-MCV/anti-CCP or anti-MCV/anti-CCP are usefully serologic tests for the diagnosis of RA in Chinese patients.

Topics: Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Case-Control Studies; China; Citrulline; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Glucose-6-Phosphate Isomerase; Humans; Keratins; Male; Middle Aged; Nephelometry and Turbidimetry; Peptides, Cyclic; Predictive Value of Tests; Serologic Tests; Vimentin; Young Adult

To assess the genetic effect on the occurrence of rheumatoid arthritis (RA) associated autoantibodies.. A co-twin control study of 27 monozygotic (MZ) and 51 dizygotic same sexed (DZss) RA discordant twins.. The probandwise concordance rate of anti-keratin antibodies (AKA), anti-cyclic citrullinated peptide antibodies (ACPA), IgA- and IgM rheumatoid factor (IgA-RF and IgM-RF). The odds ratio for these autoantibodies based on both conditional and unconditional logistic regression adjusting for the two major genetic risk factors as well as smoking.. The probandwise concordance rates (95% CI) of ACPA, AKA, IgM-RF and IgA-RF were 78.6 (55.4-92.4), 16.7 (0.6-58.4), 30.0 (7.3-60.6), 42.1 (14.5-71.1) in MZ twins and 25.0 (10.3-44.4), 0.0 (0.0-27.7), 10.5 (1.4-31.5) and 22.2 (6.8-45.0) in DZss twins. In twin pairs discordant for both RA and autoantibodies the OR of ACPA, AKA, IgM-RF and IgA-RF was 5 (0.5-236.5) 9 (1.3-394.5) 272 (3.5-593.2) and 10 (1.4-434.0) in MZ twin pairs and 17 (4.4-146.1) 20 (3.2-828.0) 33 (5.5-1342.4) and 577 (7.4-1149.2) in DZss twin pairs. In multiple logistic regression analysis on ACPA, the MZ/DZ OR was 21.1 (3.3-213.5) when adjusting for age, sex, ever smoking, PTPN22 1858 T-allele, Shared Epitope (SE) and SE-smoking interaction.. There is a genetic contribution to ACPA generation independent of both SE and PTPN22 1858 T-allele. Environmental factors may trigger the expression of IgA-RF, ACPA and AKA in healthy persons who are predisposed to RA.

Topics: Aged; Alleles; Arthritis, Rheumatoid; Autoantibodies; Diseases in Twins; Female; Genetic Predisposition to Disease; Genotype; HLA-DRB1 Chains; Humans; Keratins; Logistic Models; Male; Middle Aged; Multivariate Analysis; Peptides, Cyclic; Polymorphism, Single Nucleotide; Protein Tyrosine Phosphatase, Non-Receptor Type 22; Rheumatoid Factor; Smoking; Twins, Dizygotic; Twins, Monozygotic

It is well documented that in early rheumatoid arthritis, anti-CCP antibodies have better diagnostic value than rheumatoid factors and anti-keratin antibodies. However, their role is less well defined in patients with established or long duration disease.. To evaluate and to compare diagnostic performances of anti- CCP, anti-keratin, IgM and IgA rheumatoid factors in established rheumatoid arthritis.. In a cross-sectional study, 90 patients with established rheumatoid arthritis and 100 controls were tested for these autoantibodies. The association of these markers with disease activity and severity was investigated. The sensitivity and specificity were calculated for each of four tests, using the clinical diagnosis as the gold standard.. The anti-CCP and IgM rheumatoid factor exhibited the best diagnostic value. None of the tested antibodies had any significant association with the disease activity score (DAS28). After adjustment by multiple linear regression, only anti-CCP positivity was found to be significantly associated with erosive disease.. In long duration rheumatoid arthritis, anti-CCP and IgM rheumatoid factor have similar diagnostic value. However anti- CCP are useful in seronegative patients. They are also a reliable marker of severe erosive disease.

Topics: Arthritis, Rheumatoid; Autoantibodies; Cross-Sectional Studies; Female; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic

Antibodies against citrulline-containing epitopes, such as antiperinuclear factor (APF), antikeratin antibodies (AKA), antifilaggrin antibodies, and anticyclic citrullinated peptide (anti-CCP) antibodies, are specific in rheumatoid arthritis (RA). Detection of APF, AKA, and anti-CCP has been widely used in clinical practice. However, studies on combined detection of these anti citrullinated protein antibodies (ACPA) in the significance of diagnosing RA have been limited. We aimed to detect APF, AKA, and anti-CCP antibodies and to evaluate the significance of combined detection of these ACPA in RA.. A total of 551 patients with arthritic disorders, 304 with RA and 247 with other rheumatic diseases, were selected at the Department of Rheumatology and Immunology during the past 2 years. AKA and APF were tested by indirect immunofluorescence assay. Anti-CCP was detected using the second-generation ELISA kit.. The sensitivities of anti-CCP, AKA, and APF tests for RA were 76.2%, 43.4%, and 34.5%, respectively, while the specificities were 96.0%, 98.4%, and 99.6%. The combination of anti-CCP, AKA, and APF positivity had the highest specificity (100%), but it yielded a low sensitivity (28.3%). When 2 of the 3 ACPA were positive, the sensitivity and specificity were 48.4% and 99.2%, respectively. When either anti-CCP or AKA or APF was positive, sensitivity increased to 77.3%, but specificity decreased to 94.7%.. Anti-CCP was the most valuable marker in the diagnosis of RA, among the 3 ACPA. Combined detection of anti-CCP, AKA, and APF did not increase the diagnostic capability for RA.

Topics: Adult; Aged; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Female; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic; Sensitivity and Specificity

Keratin is the main component of cellular intermediate filaments, and its post-translational modification plays an important role in cell differentiation and apoptosis, as well as disease states. The conversion of peptidylarginine to citrulline, termed citrullination, is particularly involved in the pathogenesis of rheumatoid arthritis (RA). Immunohistochemistry using an antibody mixture that broadly recognized various keratin forms detected cytokeratin in many cells in the area lining the synovial membrane of RA. Furthermore, double immuno-florescent labeling showed that the cells expressing cytokeratin were also positive for citrulline when they were in the vicinity of extracellular deposits or approached the exterior of the synovial membrane. Western blot analysis demonstrated citrullination of keratin purified from RA synovial tissue by immuno-precipitation. The above results indicate the presence of citrullinated cytokeratin in synovial membranes in RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; Blotting, Western; Citrulline; Female; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Synovial Membrane

To explore the diagnostic significance of anti-cyclic citrullinated peptide (CCP) antibody (anti-CCP), antikeratin antibody (AKA) and rheumatoid factor (RF) for predicting articular erosions in patients with rheumatoid arthritis (RA).. One hundered and fifty eight RA patients were devided into 2 groups [limited radiographic damage group (Group 1) and severe radiographic damage group (Group 2)] based on the Larsen's score system. Enzyme linked immunosorbent assay, indirect immunofluorescence and rate naphelometry were used to measure anti-CCP, AKA and RF, respectively.. The sensitivity and specificity of Anti-CCP, AKA and RF for detecting RA were 49% and 94%, 50% and 93%, and 79% and 67%, respectively. The specificity increased when any two markers were combined. The patients with severe radiographic damage had higher positive rates of these three antibodies than the patients with limited radiographic damage. Anti-CCP had the highest OR (6.71) for predicting articular erosions in RA patients. The logistic regression analysis showed a strong correlation between anti-CCP, AKA, CRP or cutaneous nodules and the severity of articular erosions. Anti-CCP had the strongest correlation with the severe radiographic damages.. Anti-CCP has advantages over the other two antibodies in diagnosing RA. However, the diagnostic accuracy can be improved when anti-CCP is combined with AKA or RF. Anti-CCP and AKA have strong correlations with severe articular erosions, which will be helpful for predicting the outcomes of RA.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Female; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic; Predictive Value of Tests; Rheumatoid Factor; Sensitivity and Specificity; Severity of Illness Index; Young Adult

To analyze the clinical characteristics of interstitial pulmonary fibrosis (IPF) in patients with Rheumatoid arthritis (RA).. We retrospectively analyzed 198 RA patients with or without IPF. Characteristics of RA-IPF in clinical and lab data were analyzed. Age, duration of disease, clinical and laboratory parameters, history of smoking and medicine were compared between the patients with and without IPF.. (1) Among the 198 RA patients, 15.2% (30/198) were found with IPF. 100% RA-IPF patients had HRCT findings. However, 63.3% (19/30) had positive findings in chest X-ray, and only 46.7% (14/30) had the complaints of cough and short breath. Velcro rales were found in 50.0% (15/30) patients with IPF and no acropachy occurred. Only one patient suffered from hypoxemia. IPF presented after the joint symptoms in most patients. (2) RA-IPF patients were older than those without IPF [(65.50 +/- 9.71) vs (55.22 +/- 12.98) years, P<0.01]; Higher positivity of anti-keratin antibodies (AKA) were found in RA-IPF compared to patients without IPF (61.5% vs 35.9%, P=0.014). Furthermore, the levels of anti-cyclic citrullinated peptide (CCP) antibody were significantly higher in RA-IPF [(4.38 +/- 2.08) vs (3.20 +/- 2.12), P=0.01]. No differentiation of duration of disease, history of smoking and medicine, IgM rheumatoid factor, IgG rheumatoid factor, anti-nuclear antibody, anti-SSA antibody and levels of immunoglobins and complements were found between the two groups of RA patients with and without IPF.. The clinical symptoms of IPF in RA patients are mild and more common in older patients. AKA and anti-CCP antibody might be important antibodies associated with RA-IPF.

Topics: Aged; Antibodies; Arthritis, Rheumatoid; Female; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic; Pulmonary Fibrosis; Retrospective Studies

Serum antibodies reactive with the keratin layer of rat esophagus (AKA) were found in 46 of 80 (57.5%) rheumatoid arthritis (RA) patients. In contrast, AKA were present in only 7 of 82 (9.5%) patients with other types of rheumatic disorders and in 2 of 47 (4.2%) healthy subjects. AKA were not specific for RA, however, because in the former group, AKA were present in 4 of 20 (20%) systemic sclerosis patients and in 3 of 12 (25%) ankylosing spondylitis patients. AKA belong predominantly to the IgG class and are complement fixing. Although found in some RA joint fluids, AKA were not selectively concentrated in the joint fluid. Absorption of RA serum with type I human collagen or with human epidermal keratin did not remove AKA activity. The frequency of AKA in RA patients both negative and positive for DR4 was equal. There was no relationship between the frequency of AKA and the occurrence of other serum autoantibodies such as antibodies to intermediate filaments, smooth muscle, and nuclear antigens. Serum antibody reactive with human stratum corneum found in patients with psoriatic arthritis was shown to be different from AKA. Rabbit antiserum to human keratin did not inhibit the reaction of AKA against the keratin layer of rat esophagus. Autoimmunity to structural proteins including collagen, vimentin intermediate filaments, smooth muscle antigens, and keratin is a characteristic feature of RA.

Topics: Animals; Arthritis, Rheumatoid; Autoantibodies; Esophagus; History, 20th Century; Humans; Keratins; Rats; Seroepidemiologic Studies

Autoantibodies in rheumatoid arthritis (RA) are useful both for diagnosis and prognosis. Antibodies directed against citrullinated antigens have recently been shown to predict development of RA as well as poor outcome in early arthritis. Data on their role in established RA is limited. We studied the association of various autoantibodies in RA with its severity.. A total of one hundred and twenty nine-patients with established RA was enrolled and sera were collected and stored at -70 degrees C. Data regarding erosions, deformities, and extra-articular features were collected. IgM rheumatoid factor (RF) was measured using nephelometry and value above 20 U was considered positive. IgA RF was measured by enzyme-linked immunosorbent assay (ELISA) and value above the mean+/-2 SD of normal healthy control was taken as positive. Anti-keratin antibody (AKA) was detected by indirect immunofluorescence assay using rat esophagus as substrate. Anti-cyclic citrullinated peptide (CCP) antibodies were measured by commercial ELISA and a value above 5 U was considered as positive.. The prevalence of various autoantibodies was: IgM RF 82.2%, anti-CCP antibodies 82.2%, AKA 51.9%, and anti IgA RF 45%. The concordance rate of anti-CCP antibodies with IgM RF was 83%, with AKA 68%, and with IgA RF 60.5%. All but one patient positive for AKA were positive for anti-CCP antibodies. The presence of IgM RF, AKA, and anti-CCP antibody was associated with joint erosions and deformities. None of the antibodies had any association with presence of extra-articular features. No association of IgA RF was seen with erosions, deformities, or extra-articular features. Among 23 seronegative RA patients, 11 were positive for anti-CCP antibodies and 6 were AKA positive. The presence of anti-CCP antibodies was associated with presence of deformities (p<0.05).. Anti-CCP antibodies are present in majority of patients with established RA including seronegative patients. Both anti-CCP and AKA, in addition to conventional marker like IgM RF, are associated with severe erosive disease.

Topics: Adult; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Health Status; Humans; Immunoglobulin A; Immunoglobulin M; Keratins; Male; Peptides, Cyclic; Prognosis; Radiography; Rheumatoid Factor; Severity of Illness Index

To specify significance of some serological markers for diagnosis and x-ray prognosis of rheumatoid arthritis (RA).. A total of 115 RA patients with the disease history not longer than 4 years were examined for serum antibodies to cyclic citrullated peptide (ACCP), rheumatoid factor (RF), antikeratine antibodies (AKA) using enzyme immunoassay and indirect immunofluorescence.. ACCP, AKA, IgA-RF, IgM-RF were detected in 79.15%, 47.8%, 64.3%, 89.6% patients, respectively. ACCP was found to be directly correlated with negative x-ray changes in hand and foot joints. ACCP specificity reached 97%, the highest specificity (up to 100%) being in determination of RF and ACCP.. ACCP is an independent factor increasing significance of x-ray indices and thus allowing prognosis of x-ray outcome of RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; Arthrography; Autoantibodies; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic; Predictive Value of Tests; Rheumatoid Factor; Sensitivity and Specificity; Severity of Illness Index

To investigate the prevalence of anti-cyclic citrullinated peptide (anti-CCP) and anti-keratin antibodies (AKA) in patients with primary Sjögren's syndrome.. 149 patients with a diagnosis of primary Sjögren's syndrome according to the European/American consensus criteria were recruited from three French medical centres. The presence of anti-CCP was determined by enzyme linked immunosorbent assay and of AKA antibodies by indirect immunofluorescence. Radiographs of hands and feet were evaluated at the time of anti-CCP analysis.. Six patients with radiological erosions and nine patients with non-erosive arthritis fulfilling ACR criteria for rheumatoid arthritis were thought to have rheumatoid arthritis and secondary Sjögren's syndrome, while 134 were considered to have primary Sjögren's syndrome (mean (SD) disease duration, 11.1 (6.6) years). Of these, 80 tested positive for IgM rheumatoid factor (RF) (59%), 10 (7.5%) for anti-CCP, 7 (5.2%) for AKA, and 5 (3.7%) for both anti-CCP and AKA. There was no difference in clinical and biological features, including prevalence of RF, between anti-CCP positive and negative patients. The nine Sjögren patients with non-erosive arthritis, fulfilling ACR criteria for rheumatoid arthritis, were all CCP positive. Their response to disease modifying antirheumatic drugs could be different from classical rheumatoid patients.. Most patients with primary Sjögren's syndrome are negative for AKA and anti-CCP, but positive test results should not rule out this diagnosis. Anti-CCP positive patients, who may be prone to developing rheumatoid arthritis, require cautious clinical and radiographic follow up.

Topics: Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Female; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic; Radiography; Rheumatoid Factor; Sjogren's Syndrome

This work aims to clarify the histogenesis of the cells forming RA pannus: the pannocytes.. 15 patients with seropositive RA; 5 controls with post-traumatic knee effusion and 5 with OA knee effusion were included in the study. Synovial tissues and fluids, collected during diagnostic arthrocentesis, were used as a source of cells to be cultured. Viable staining and cytocentrifugation were performed. Cell phenotype was investigated by immunofluorescence assays after different culture periods. Cells were also studied by immunohistochemistry to determine the presence of CD5, CD68:KP-1, CD68:PG-M1, vimentin, cytokeratin, a-SM-Actin.. Cells derived from RA samples were sub-divided into two population of lymphocyte-like and macrophage-like cells. Phenotypical characteristics of the first one were analysed after 6 days of culture and suggested they were T lymphocytes. The other population could grow in vitro for undefined time resembling the neoplastic-like proliferation previously described for pannocytes. Phenotypic characterization excluded that these cells were lymphocytes, monocyte-macrophages, fibroblasts, myofibroblasts, endothelial cells or keratinocytes. On the contrary, immunohistochemistry demonstrated that 100% of pannocytes were vimentin positive and 75% of these cells expressed also CD68:KP-1. CONCLUSIONS. The results exclude that pannocytes originate from monocyte-macrophages or from fibroblasts, but strongly support the hypothesis that they belong to the family of primitive embryonal connective tissue-forming cells (residue of the primitive mesenchymal tissue).

Topics: Actins; Adult; Aged; Antigens, CD; Arthritis, Rheumatoid; Case-Control Studies; Cells, Cultured; Female; Fluorescent Antibody Technique; Humans; Immunohistochemistry; Keratins; Knee Injuries; Male; Mesoderm; Middle Aged; Phenotype; Synovial Fluid; Synovial Membrane; Vimentin

The objective of this study was to investigate the frequency of antibodies against cyclic citrullinated peptides (anti-CCP) and keratin (AKA) in patients with rheumatoid arthritis (RA) as well as in patients with primary Sjögren's syndrome (pSS) and Wegener's granulomatosis (WG), who may present with rheumatoid factor (RF)-positive arthritis. The study group consisted of 46 patients with RA (26 patients were negative for RF), 32 with pSS, 22 with WG, and 40 healthy controls. The RF, anti-CCP, and AKA were detected in serum using the latex agglutination test, enzyme-linked immunosorbent assay, and indirect immunofluorescence, respectively. The agreement between those tests was evaluated by kappa test. No positive result for AKA was detected in pSS and WG patients, and anti-CCP was found in only one patient with pSS. The results of kappa tests were low, varying between 0.25 (RF-anti-CCP) and 0.02 (RF-AKA). The sensitivity and specificity values were 43 and 44% for RF, 65 and 98% for anti-CCP, and 58 and 100% for AKA, respectively, in RA patients. In the RF-negative RA group, AKA was found to have a high frequency (55%) in comparison to anti-CCP (38%). Seropositivity was found to be 87% for any one of the three autoantibodies tested in RA patients. With a higher specificity, values for RA, anti-CCP, and AKA seem to be helpful for the differential diagnosis of patients with RF-positive arthritis, which may include patients with WG and pSS, and screening of all three antibodies may increase the diagnostic performance.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Female; Granulomatosis with Polyangiitis; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic; Reproducibility of Results; Rheumatoid Factor; Sensitivity and Specificity; Sjogren's Syndrome

Our objective was to (i) compare FIDIS Rheuma, a new multiplexed immunoassay designed for simultaneous detection of IgM class rheumatoid factors (RF) directed against Fc determinants of IgG from humans and animals, with agglutination and ELISA (conventional methods) and (ii) evaluate the clinical sensitivity and specificity of biological markers for rheumatoid arthritis (RA). To do this, FIDIS technology was employed using the Luminex system. It consists of distinct color-coded microsphere sets, a flow cytometer, and digital signal processing hardware and software. Agglutination and ELISA tests were performed with commercial kits. The study included 134 samples from RA patients and 105 from healthy blood donors. For human specificity, we compared FIDIS with latex agglutination and ELISA. Relative sensitivities were 98.9% and 88.5% and specificities were 90.2% and 94.6%, respectively. For animal specificity, we compared FIDIS with Waaler-Rose and ELISA. The results were 84.9% and 71.9% for the sensitivities and 97.5% and 98.4% for the specificities, respectively. Detection of IgG anti-CCP by ELISA and IgG antikeratin by immunofluorescence was also determined in order to compare their clinical sensitivity and specificity with IgM-RF, according to the method used. The results were: IgG anti-CCP 72.3%, 97.2%; IgG antikeratin 36.6%, 100%; latex agglutination 66.4%, 97.2%; Waaler-Rose 55.9%, 96.3%; FIDIS human 73.9%, 92.1%; FIDIS animal 49.2%, 97.2%; ELISA human 93.2%, 95.5%; and ELISA animal 74.6%, 91.3%. The results showed the efficiency of FIDIS with analytical performance equivalent to the conventional methods, but having the advantage of giving quantitative results (IU/mL).

Topics: Agglutination Tests; Animals; Antibody Specificity; Arthritis, Rheumatoid; Biomarkers; Case-Control Studies; Citrulline; Enzyme-Linked Immunosorbent Assay; Epitopes; Evaluation Studies as Topic; Fluorescent Antibody Technique, Indirect; Humans; Immunoassay; Immunoglobulin G; Immunoglobulin M; Keratins; Latex Fixation Tests; Peptides, Cyclic; Rabbits; Reagent Kits, Diagnostic; Rheumatoid Factor; Sensitivity and Specificity; Species Specificity

To assess diagnostic informative value of specific autoantibodies (AAB)--antikeratin antibodies (AKA), antiperinuclear factor (APF) and antibodies to cyclic peptide containing citrullin (CCP) from the family of antifilaggrine autoantibodies (AFA)--in rheumatoid arthritis (RA).. A total of 121 patients with RA and 45 patients with seronegative spondylarthropathies. Rheumatoid factor was detected with latex agglutination. AKA and APF were estimated with indirect immunofluorescence the substrate of which was series frozen sections of rat esophagus in the middle third of 4 mcm and cells of the epithelium of the internal surface of healthy donor's cheek. For detection of antibodies to cyclic peptide, the test DIASTAT Anti-CCP ELISA (Axis Shield, Great Britain) was made.. The RF was detected in 67.8% patients with RA; AKA, APF and antibodies to CCP--in 43.6, 52.9 and 68.0% patients, respectively. AKA were most specific for RA (100%) while the RF was least specific among the AAB studied (87%). Simultaneous use of RF and AFA allows AAB detection in 84% RA patients at early stages of the disease. AFA were detected in patients with high clinico-laboratory activity of the process, high indices of functional joint insufficiency. 95% of all cases of destructive arthritis were detected in patients with RF, AKA, APF and antibodies to CCP.. For RA patients it is necessary to determine both RF and AFA. Detection of AFA allows early diagnosis of RA as well as to single out patients with more aggressive course of the disease and unfavourable prognosis.

Topics: Adult; Aged; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Female; Filaggrin Proteins; Fluorescent Antibody Technique, Indirect; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Rheumatoid Factor; Severity of Illness Index

The objective of the study was to determine the diagnostic value for rheumatoid arthritis (RA) of anti-filaggrin autoantibodies (autoAb) recognizing citrullinated recombinant rat filaggrin (ACRF) in community cases of very early arthritis. To evaluate the diagnostic value of ACRF, were studied sera from patients with different classified rheumatic diseases and healthy subjects (group 1, n= 422) and 314 community cases of very early arthritis (group 2) that were classified as RA (n = 176), non-RA (n = 63) and undifferentiated (n = 75) arthritides after 1 years of follow-up. ACRF were measured using a new ELISA, with results expressed as the difference between the OD value obtained on citrullinated minus that on noncitrullinated rat filaggrin (differential ACRF; dACRF). For both groups, rheumatoid factors (RF), anti-keratin autoAb (AKA) and anti-perinuclear factor (APF) were tested; for group 2, anti-CCP autoAb were also tested. Different reactivity patterns against citrullinated and noncitrullinated filaggrin were observed. Almost all sera reacting with citrullinated but not noncitrullinated filaggrin were from RA patients. Among RA and non-RA sera that recognized both forms of filaggrin, a positive result was obtained only with RA sera. For groups 1 and 2, dACRF sensitivity was 58.4% and 30.7%, and specificity for RA was 99.5% and 98.4%, respectively. In group 2, dACRF specificity for RA was better than that of RF (92.1%), APF (95.2%), AKA (96.8%) and anti-CCP (95.2%). dACRF positive predictive value was high (98.2) and close to that given by the concomitant positivity of RF and anti-CCP autoAb. Despite a high positive correlation between AKA, APF, anti-CCP and dACRF test results, they were complementary since some sera were positive for only one test. Thus, in a community setting, anti-citrullinated rat filaggrin reactivity detected by a new ELISA, whose originality is based on the difference between serum's reactivities on the citrullinated and native forms of filaggrin, had a higher diagnostic value for RA than other autoAb.

Topics: Adult; Aged; Aged, 80 and over; Animals; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Citrulline; Enzyme-Linked Immunosorbent Assay; Female; Filaggrin Proteins; Fluorescent Antibody Technique, Indirect; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Rats; Recombinant Proteins; Rheumatoid Factor; Sensitivity and Specificity

Anti-filaggrin antibodies (AFA) are among the most specific antibodies for rheumatoid arthritis, so procedures for their detection should be included in early biological diagnoses. AFA can be detected by indirect immunofluorescence (anti-keratin antibodies, AKA) or by new enzyme immunoassays (EIA). Their comparative performance needs to be established.. To compare these technical procedures to optimise the serological diagnosis of rheumatoid arthritis.. Results obtained using AKA and EIA were compared in 271 sera from 140 patients with rheumatoid arthritis at various stages, 98 patients with other autoimmune diseases, and 33 healthy subjects. EIA were successively undertaken with citrullinated linear filaggrin peptide (home made EIA) or cyclic citrullinated peptide (CCP2, commercial kits). Rheumatoid factor (RF) was assessed by EIA in all patients.. Anti-CCP2 kits showed the best sensitivity and specificity (65% and 96%, respectively). Among the 140 patients with rheumatoid arthritis, those with very recent disease (less than six months' duration, n = 21) were studied as a separate group. In this group, the sensitivity of anti-CCP2 kits decreased to approximately 50%. Nevertheless this assay remained the most accurate when compared with AKA or home made EIA using linear filaggrin peptides. The combination of anti-CCP2 and RF only slightly increased the sensitivity of the diagnosis of very early rheumatoid arthritis.. Kits using citrullinated cyclic peptides (CCP2) were more suitable than either AKA or EIA using linear filaggrin peptides for the diagnosis of early rheumatoid disease.

Topics: Antibodies; Arthritis, Rheumatoid; Biomarkers; Citrulline; Filaggrin Proteins; Fluorescent Antibody Technique, Indirect; Humans; Immunoenzyme Techniques; Immunoglobulin G; Intermediate Filament Proteins; Keratins; Lupus Erythematosus, Systemic; Reagent Kits, Diagnostic; Rheumatoid Factor; Sensitivity and Specificity; Sjogren's Syndrome

To determine whether raised levels of antibodies to CK18 in patients with RA are associated with ischaemic heart disease (IHD).. IgA, IgG, and IgM antibodies to CK18 were measured by enzyme linked immunosorbent assay (ELISA) in patients with RA with (n = 34) or without (n = 28) IHD. The relationship between CK18 antibody levels and markers of inflammatory and/or cardiovascular disease was examined.. Initial analysis showed that IgG antibody levels to CK18 were higher in patients with RA with IHD than in those without (50.1 v 34.5 AU, p = 0.047), although significance was lost after correction for multiple comparisons. Further analysis showed a significant difference (p = 0.015) between patients with IHD and a positive family history, and patients without IHD and a negative family history (53.7 v 29.0 AU, Kruskal-Wallis multiple comparison Z value test). There was also a significant trend of increasing 10 year cardiovascular risk with increasing CK18 IgG antibody levels (p = 0.01). No association was found between CK18 antibody levels and conventional markers of inflammation or cardiovascular disease, but an association was found between levels of CK18 IgG and IgG antibodies to cytomegalovirus (CMV) (Spearman's r(s) = 0.379, p(corr) = 0.04). No evidence for cross reactivity of CK18 antibodies with CMV antigens was found.. Levels of IgG antibodies to CK18 are raised in patients with RA with IHD, particularly if they also have a positive family history. This may reflect damage to CK18 containing cells in the cardiac vasculature and/or in atherosclerotic plaques, and may be a useful additional marker for the identification of patients with, or likely to develop, IHD.

Topics: Antibodies; Antibodies, Viral; Arthritis, Rheumatoid; Biomarkers; Cross Reactions; Cytomegalovirus; Enzyme-Linked Immunosorbent Assay; Family Health; Female; Humans; Keratins; Male; Middle Aged; Myocardial Ischemia; Risk Factors; Sensitivity and Specificity; Sex Factors

Chronic hepatitis C virus (HCV) has been linked to extrahepatic autoimmune phenomena. In addition a variety of autoantibodies were found in patients with HCV. This study was performed to assesss the clinical relevance of antikeratin antibodies in rheumatoid arthritis (RA) and in patients with symmetric polyarthritis associated with hepatitis C infection. Serum antikeratin antibodies were evaluated in 3 different groups of patients; all were rheumatoid factor (RF) seropositive: Group 1: 31 patients with HCV associated symmetric polyarthralgia or arthritis. Group 2: 28 patients with RA (modified ACR criteria for probable RA). Group 3: 16 patients with autoimmune disorders other than RA. Seventeen healthy individuals matched for age and sex served as controls. In our study, 75 patients who were rheumatoid factor positive (measured by ELISA, the cutoff was established to 20 U/mL) were tested for antikeratin antibodies using an indirect immunofluorescence technique with 1:10 serum dilution. Antikeratin antibodies were detected in 18/28 (64%) patients with true RA and only 3/31 (9%) patients with HCV-related arthritis (p < 0.0001). Antikeratin antibodies were observed in 3/16 (18%) patients of group 3 (p < 0.05). Antikeratin antibodies were not found in the sera of the healthy controls.

Topics: Arthritis; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Case-Control Studies; Female; Fluorescent Antibody Technique, Indirect; Hepatitis C, Chronic; Humans; Immunoglobulin G; Keratins; Male; Rheumatoid Factor

To study the value of antibodies to citrullinated proteins/peptides for predicting joint outcomes in patients with recent onset rheumatoid arthritis (RA).. 191 patients with RA onset within the past year were followed up prospectively for five years. Serum samples obtained from 145 patients at baseline before disease modifying antirheumatic drug treatment were examined using three anticitrullinated protein/peptide antibody assays: antiperinuclear factor (APF) by indirect immunofluorescence (IIF), antikeratin antibodies (AKA) by IIF, and anti-cyclic citrullinated peptide (CCP) antibodies by enzyme linked immunosorbent assay (ELISA). Radiographs of the hands and feet taken at baseline and after three and five years were evaluated using Sharp scores modified by van der Heijde.. Anti-CCP ELISA was positive in 58.9% of patients. APF/anti-CCP agreement was 77%. The likelihood of a total Sharp score increase after five years was significantly greater among patients with anti-CCP antibodies (67%; odds ratio (OR) 2.5; 95% confidence interval (95% CI) 1.2 to 5.0) or APF (57%; OR 2.4; 95% CI 1.2 to 4.9) but not rheumatoid factor (RF; OR 0.7; 95% CI 0.3 to 1.5). Mean values for radiographic damage, erosion, and joint narrowing scores at the three times were significantly higher in patients with anti-CCP or APF than in those without. AKA did not significantly predict radiographic damage. In separate analyses of patients with and without RF, anti-CCP or APF was better than RF for predicting total joint damage and joint damage progression after five years.. Antibodies to citrullinated proteins/peptides determined early in the course of RA by APF IIF or anti-CCP ELISA are good predictors of radiographic joint damage. Further studies of clinical, laboratory, and genetic parameters are needed to improve RA outcome prediction in clinical practice.

Topics: Adult; Aged; Antibodies, Antinuclear; Antirheumatic Agents; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Citrulline; Disease Progression; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Peptides; Predictive Value of Tests; Prognosis; Prospective Studies; Radiography; Sensitivity and Specificity; Severity of Illness Index

To evaluate a contribution of selected laboratory parameters for a prediction of progressive and erosive development in patients with early rheumatoid arthritis (RA).. In a prospective study baseline levels of antibodies to cyclic citrullinated peptide (anti-CCP), IgM, IgA, and IgG rheumatoid factors (RFs) were measured by enzyme linked immunosorbent assay (ELISA) in 104 patients with RA with disease duration <2 years. Antikeratin antibodies (AKA) and antiperinuclear factor (APF) were detected by indirect immunofluorescence. Patients were divided into two groups based either on the presence or absence of erosions or according to progression of Larsen score at the end of the 24 months' follow up.. Sixty seven (64%) patients developed radiographic erosions, 49 (47%) had progression in Larsen score, and 36 (35%) progressed by more than 10 Larsen units. Significant differences in erosions and progression between the two groups were detected for anti-CCP, AKA, APF, IgM RF, IgA RF, and IgG RF. Baseline Larsen score correlated significantly with anti-CCP, IgM RF, and IgA RF levels, and all measured antibodies correlated with the progression >10 units. The combination of anti-CCP and IgM RF increased the ability to predict erosive and progressive disease.. The data confirmed that measurement of anti-CCP, AKA, APF, and individual isotypes of RFs was useful for prediction of structural damage early in the disease course. Combined analysis of anti-CCP and IgM RF provides the most accurate prediction.

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Disease Progression; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Keratins; Peptides, Cyclic; Predictive Value of Tests; Prospective Studies; Radiography; Rheumatoid Factor; Severity of Illness Index

To explore the diagnostic value of anti-cyclic citrullinated peptide antibody (anti-CCP) detected by ELISA in patients with rheumatoid arthritis (RA).. The synthesized cyclic citrullinated peptide was used as substrate for ELISA. Anti-CCP antibody was detected by ELISA in 191 patients with RA, 132 with rheumatic diseases other than RA, and 98 with nonrheumatic diseases. The antiperinuclear factor (APF), anti-keratin antibody (AKA), rheumatoid factor (RF), and HLA-DR4 gene complex were also tested in each RA patient. The results of these tests were compared with anti-CCP antibody to examine the correlation between them.. Ninety (47.1%) patients with RA, 4 (3.0%) with other rheumatic diseases, and 2 (2.0%) with nonrheumatic diseases were found to be anti-CCP antibody positive by ELISA. The sensitivity of anti-CCP antibody was 47.1%, with a high specificity (97.4%) in RA. Anti-CCP antibody correlated with APF, AKA, RF, and HLA-DR4 gene complex.. A new modified anti-CCP antibody test had a moderate sensitivity (47.1%) but a high specificity (97.4%) in patients with RA and was found as a valuable supplement to diagnosis of RA. Anti-CCP correlated with APF, AKA, RF, and HLA-DR4 gene complex, but did not completely overlap with them. Anti-CCP antibody could be regarded as a new diagnostic marker for RA.

Topics: Adolescent; Adult; Aged; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Citrulline; Enzyme-Linked Immunosorbent Assay; Female; HLA-DR4 Antigen; Humans; Keratins; Male; Middle Aged; Peptides, Cyclic; Predictive Value of Tests; Rheumatoid Factor; ROC Curve

To compare the diagnostic values of antiperinuclear factor (APF), antikeratin antibody (AKA), and anti-cyclic citrullinated peptides (anti-CCP) to discriminate between patients with and without rheumatoid arthritis (RA) and to determine the diagnostic value of anti-CCP used alone or with other tests.. Two hundred and seventy patients with early arthritis underwent standardized investigations in 1995-1997. The clinical utility of APF, AKA, and anti-CCP in first-visit sera was evaluated using receiver-operating characteristic curves. Combinations of anti-CCP with other laboratory tests were assessed by multiple logistic regression.. Anti-CCP, APF, and AKA were not perfectly correlated with one another. Anti-CCP with 53 UI as the cutoff was 47% sensitive and 93% specific, versus 52% and 79%, and 47% and 94%, for APF and AKA, respectively. Multiple logistic regression selected anti-CCP, AKA, IgM-rheumatoid factor (RF) ELISA, and the latex test.. Rheumatologists can routinely use 2 or 3 tests for diagnosing RA (latex and/or IgM RF ELISA, and either AKA or anti-CCP ELISA) and can add a third or fourth test when the diagnosis remains in doubt.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Citrulline; Cohort Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Keratins; Logistic Models; Male; Middle Aged; Peptides, Cyclic; Predictive Value of Tests; Rheumatology; ROC Curve

Antikeratin antibodies (AKA) and antiperinuclear factor (APF) are specific antibodies found very early in rheumatoid arthritis (RA). The objective of this eight year follow up study was to assess the value of early AKA and APF assays in predicting functional disability and cartilage damage.. In 2000, 64 patients tested for AKA and APF (antifilaggrin antibodies) between 1990 and 1993 during evaluation of early symmetric oligoarthritis or polyarthritis (suspected RA) were invited to participate in this non-concurrent cohort study. The Health Assessment Questionnaire (HAQ) score, disease activity score (DAS), and Larsen radiographic score were the primary evaluation criteria.. Twenty nine patients were re-evaluated. Clinical and laboratory data obtained in 1993 were similar in this group and in the 35 other patients. Twenty five patients had received a diagnosis of RA. Nine (31%) were rheumatoid factor (RF) positive, nine (31%) were AKA positive, and six (21%) were APF positive during the first year of the disease. APF was correlated with the Larsen score (p=0.011) and DAS (p=0.035) evaluated after a mean disease duration of 8.55 years. All APF positive patients had erosive disease. AKA was correlated with the DAS (p=0.035).. The presence of AKA or APF early in the course of RA was associated with the DAS or Larsen score eight years later. The number of patients was small, but the findings confirmed those of studies with shorter follow ups. Antifilaggrin antibodies should be included in the initial investigation of patients with RA and, when positive, should alert to a high risk of poor outcomes.

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Female; Follow-Up Studies; Humans; Keratins; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prospective Studies

To assay antifilaggrin autoantibodies, we developed an enzyme-linked immunosorbent assay (ELISA) using a "citrullinated" recombinant rat filaggrin. Our objectives were to assess its value for diagnosing rheumatoid arthritis (RA) and to compare the results with those obtained using 4 other reference methods for detection of antifilaggrin autoantibodies, including the commercially available ELISA that uses a modified "citrullinated" synthetic peptide derived from the sequence of human filaggrin (CCP-ELISA).. We analyzed 711 sera from patients with well-characterized rheumatic diseases, including 240 patients with RA. Antifilaggrin autoantibodies were detected by an ELISA using a recombinant rat filaggrin deiminated in vitro as immunosorbent (ArFA-ELISA). The results considered were the differences between the optical densities obtained on deiminated and nondeiminated proteins. Antibodies to rat esophagus epithelium were detected by indirect immunofluorescence, while antibodies to human filaggrin were detected by immunoblotting and by a recently described ELISA using a deiminated recombinant human filaggrin. Finally, CCP-ELISA was performed according to the manufacturer's recommendations.. At the titer thresholds allowing diagnostic specificities of 0.95, 0.985, and 0.99 to be reached, the diagnostic sensitivities of the ArFA-ELISA were 0.76, 0.67, and 0.65, respectively. At these 3 thresholds, the sensitivities were significantly higher than those of the 4 other tests. Despite incomplete overlapping of the 5 tests, the high diagnostic performance of the ArFA-ELISA allows us to propose this test to replace all the other methods for antifilaggrin autoantibody detection.. ArFA-ELISA appears to be the most efficient test among those available for the detection of antifilaggrin autoantibodies, in terms of diagnostic accuracy for RA. Its diagnostic performance in early RA and its prognostic value are currently under evaluation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Arthritis, Rheumatoid; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Epidermis; Female; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Rats; Rats, Wistar; Recombinant Proteins; ROC Curve; Sensitivity and Specificity

The diagnosis of rheumatoid arthritis has been hampered by the lack of a truly disease-specific serologic marker. Thus, despite its moderate specificity rheumatoid factor (RF) is still the only established marker antibody for RA and among the diagnostic criteria of the American College of Rheumatology the only serologic one. However, in recent years, several newly characterized autoantibodies have been described that may have the potential to become diagnostic indicators for RA. In particular, antibodies to citrullinated targets (anti-keratin or anti-filaggrin antibodies, respectively, antibodies to synthetic citrullinated peptides) appear to be highly specific for RA. Other potentially useful antibodies include anti-RA33 autoantibodies and antibodies to the stress protein BiP which seem to have higher specificity for RA than RF. Apart from being promising diagnostic markers these autoantibodies or the underlying cellular autoimmune reactions, respectively, may also play a role in the pathogenesis of RA.

Topics: Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Filaggrin Proteins; Heat-Shock Proteins; Heterogeneous-Nuclear Ribonucleoprotein Group A-B; Humans; Intermediate Filament Proteins; Keratins; Predictive Value of Tests; Rheumatoid Factor

To determine which laboratory test or tests at presentation best predicted a diagnosis of rheumatoid arthritis (RA) 2 years later.. Two hundred seventy patients with early arthritis seen in 7 hospitals underwent comprehensive evaluations at 6-month intervals for 2 years, when the diagnosis of RA was assessed by 5 rheumatologists. The sensitivity and specificity of each test at the first visit for discriminating between RA (38%, n = 98) and non-RA patients were determined. Optimal cutoffs for continuous tests were derived from receiver operating characteristic curves. Sensitivity and specificity of test combinations selected by multiple logistic regression were determined.. IgM rheumatoid factor (RF) by enzyme-linked immunosorbent assay, IgG-antikeratin antibody (AKA), and latex test had the strongest associations with RA. These 3 tests formed the most powerful combination for distinguishing RA from non-RA.. IgM-RF, IgG-AKA, and the latex test are the best laboratory tests for discriminating between patients with and without RA. Combining these tests slightly improves diagnostic value.

Topics: Arthritis, Rheumatoid; Autoantibodies; Clinical Laboratory Techniques; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Immunoglobulin G; Immunoglobulin M; Keratins; Latex Fixation Tests; Male; Middle Aged; Regression Analysis; Rheumatoid Factor; ROC Curve; Sensitivity and Specificity

Various viruses have been implicated in the cause and pathogenesis of rheumatoid arthritis (RA). Hepatitis C virus (HCV) infection, which has been recognised as a cause of some autoimmune diseases, and which has been described as sometimes presenting with rheumatic manifestations indistinguishable from RA, might be a candidate.. To evaluate the prevalence of HCV infection in patients with RA.. Consecutive patients with RA admitted to hospital in two departments of rheumatology were prospectively studied. Patients' serum samples were screened for the presence of anti-HCV antibodies. Patients with positive serology were further evaluated for the presence of HCV ribonucleic acid by reverse transcriptase polymerase chain reaction (RT-PCR).. 309 patients (232 women, 77 men, mean age (SD) 54.1 (14.8) years) were studied. Their mean (SD) disease duration was 74.1 (91) months. Tests for rheumatoid factors and antinuclear antibodies were positive in 213 (69%) and 114 (37%) of the patients respectively. Systemic vasculitis was found in 12 (4%) of the patients. Mean erythrocyte sedimentation rate was 36.4 (SD 30.5) mm at the first hour (normal <10 mm) and C reactive protein was 36.8 (SD 45.8) mg/l (normal range <5 mg/l), respectively, with 181(58.6%) of patients considered as having active disease. Aspartate transaminases were increased in 14 (4%) patients, and alkaline phosphatase in 14 (4%). A positive anti-HCV serology was found in two (0.65%) patients, including one with a previously diagnosed HCV infection. HCV RNA was positive by RT-PCR in one of those two patients.. A 0.65% prevalence of past or active HCV infection was found in patients with RA, which did not differ from the prevalence of HCV in the general French population. This result does not support the participation of HCV infection in the pathogenesis of RA.

Topics: Alkaline Phosphatase; Antibodies; Arthralgia; Arthritis, Rheumatoid; Enzyme-Linked Immunosorbent Assay; Female; gamma-Glutamyltransferase; Hepatitis C; Hepatitis C Antibodies; Histocompatibility Testing; HLA-DR Antigens; Humans; Keratins; Male; Reverse Transcriptase Polymerase Chain Reaction; Rheumatoid Factor; Transaminases

To examine the value of anti-cyclic citrullinated peptide (anti-CCP) antibodies, anti-keratin antibodies (AKA) and immunoglobulin M rheumatoid factors (IgM RF) in discriminating between rheumatoid arthritis (RA) and other rheumatic diseases, and to determine whether the clinical manifestations or severity of erosions in RA are associated with anti-CCP positivity.. In a cross-sectional study, we determined the concentrations or titres of these three markers in 179 RA patients and 50 controls. Erosions were quantified using the Larsen score in 129 patients.. Sensitivity was highest for IgM RF (75%), followed by anti-CCP antibodies (68%) and AKA (46%). Specificity was highest for anti-CCP antibodies (96%), followed by AKA (94%) and IgM RF (74%). A correlation with clinical manifestations and severity of erosions was observed mainly for IgM RF positivity.. With their excellent specificity, anti-CCP antibodies can be useful in establishing the diagnosis of RA, but IgM RF is a better predictor of disease severity.

Topics: Aged; Antibodies; Arthritis, Rheumatoid; Biomarkers; Citrulline; Cross-Sectional Studies; Female; Humans; Immunoglobulin M; Keratins; Male; Middle Aged; Rheumatoid Factor; Severity of Illness Index

To assess the clinical value of several serological markers in Lithuanian patients with rheumatoid arthritis (RA) compared with control patients with rheumatic disease and age matched healthy controls.. Serum samples from 96 patients with RA of approximately 8 years' duration, 90 rheumatic disease controls, and 37 healthy subjects were tested. Antikeratin antibody (AKA), antineutrophil cytoplasmic antibody (ANCA), and antinuclear antibody (ANA) titres were estimated by indirect immunofluorescence (IIF) and serum samples positive for ANA and ANCA were further studied by enzyme linked immunosorbent assay (ELISA). IgA and IgM rheumatoid factors (RF) were measured by ELISA.. A positive AKA test was highly specific for RA (diagnostic specificity 97%), being found in 44% of the patients. Although both RF tests had a higher sensitivity, they were less specific for RA. ANCA was detected in 33% of patients with RA but lacked diagnostic specificity. AKA and ANCA were associated with more erosive disease and the presence of extra-articular manifestations. Positivity for AKA, IgA RF, and ANCA was significantly associated with disease activity and worse functional capacity. However, in multiple regression analysis only positivity for AKA was significantly correlated with functional disability (p=0.0001), evaluated by the Steinbrocker functional classification, and no single marker had any relation with radiological damage.. Although AKA showed the highest disease specificity, all serological markers studied except ANA exhibited interesting associations with important clinical and paraclinical parameters of RA.

Topics: Adult; Aged; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Humans; Immunoglobulin G; Immunoglobulin M; Keratins; Male; Middle Aged; Prevalence; Regression Analysis; Rheumatic Diseases; Rheumatoid Factor

To develop a standardisable enzyme linked immunosorbent assay (ELISA), using human filaggrin, for detection of antifilaggrin autoantibodies in rheumatoid arthritis (RA). To compare the diagnostic performance of the ELISA with those of reference tests: "antikeratin antibodies" ("AKA"), and antibodies to human epidermis filaggrin detected by immunoblotting (AhFA-IB).. Two ELISAs were developed using either affinity purified neutral-acidic human epidermis filaggrin (AhFA-ELISA-pur) or a recombinant human filaggrin deiminated in vitro (AhFA-ELISA-rec) as immunosorbent. Antifilaggrin autoantibodies were assayed in 714 serum samples from patients with well characterised rheumatic diseases, including 241 RA and 473 other rheumatic diseases, using the two ELISAs. "AKA" and AhFA-IB tests were carried out in the same series of patients. The diagnostic performance of the four tests was compared and their relationships analysed.. The titres of "AKA", AhFA-IB, and the AhFA-ELISAs correlated strongly with each other. The diagnostic sensitivity of the AhFA-ELISA-rec, which was better than that of AhFA-ELISA-pur, was 0.52 for a specificity of 0.95. This performance was similar to those of "AKA" or AhFA-IB. However, combining AhFA-ELISA-rec with AhFA-IB led to a diagnostic sensitivity of 0.55 for a specificity of 0.99.. A simple and easily standardisable ELISA for detection of antifilaggrin autoantibodies was developed and validated on a large series of patients using a citrullinated recombinant human filaggrin. The diagnostic performance of the test was similar to that of the "AKA" and AhFA-IB. Nevertheless, combining the AhFA-ELISA-rec with one of the other tests clearly enhanced the performance.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoantibodies; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Filaggrin Proteins; Humans; Immunoblotting; Immunologic Tests; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Sensitivity and Specificity; Statistics, Nonparametric

To elucidate the possibility that autoantibodies to filaggrin, detected in patients with early RA (having a disease duration of not more than one year), may predict joint destruction assessed after five years of observation.. This is a 5 yr extension of a previous study (1) of 112 consecutive patients with early RA. Serum antifilaggrin autoantibodies were detected by immunoblotting (AFA) and by indirect immunofluorescence ("AKA"). DAS28, pain on a VAS. HAQ, and CRP were measured. Plain X-ray films were taken from hands and forefeet and a Larsen score was calculated.. Ninety-two of the original 112 patients had baseline X-rays available and constituted the study material. At 5 year follow-up, 67 of these 92 have been assessed and for 63 of these X-rays were available. For the whole patient material, significant radiological progression, measured by Larsen scores, occurred while disease activity and function (pain VAS, DAS28, CRP, and HAQ) improved significantly over five years. The groups of patients having AFA or "AKA" at baseline had significantly (p=0.006 and p<0.001, respectively) higher Larsen scores five years later than the groups without these antibodies. No clear relation of these antibodies to disease activity or function was demonstrated, except that the group of patients with "AKA" had significantly higher median CRP (p=0,003) after five years.. The present study shows that antifilaggrin autoantibodies may predict radiological progression. The prognostic value of these antibodies will be further evaluated in relation to other potential markers in a larger patient material.

Topics: Arthritis, Rheumatoid; Arthrography; Autoantibodies; C-Reactive Protein; Disability Evaluation; Disease Progression; Female; Filaggrin Proteins; Fluorescent Antibody Technique, Indirect; Foot; Hand; Health Status; Humans; Immunoblotting; Intermediate Filament Proteins; Joints; Keratins; Male; Middle Aged; Pain; Rheumatoid Factor; Severity of Illness Index; Surveys and Questionnaires

Little data is available on the prevalence and incidence of rheumatoid arthritis (RA) or the genetic and environmental factors that influence RA risk and severity in non-Caucasian populations. The prevalence of RA in Caucasians and some Native American populations is 1% or more; in contrast, low prevalences of RA have been reported in some African populations. We determined the hospital incidence (HI) and period prevalence (PP) of RA in African Colombians in Quibdo, Colombia, by using data collected at the Hospital San Francisco de Asis, a primary-to-tertiary care center. Genetic and immunologic studies of factors that influence RA risk and severity, such as HLA genes, immunoglobulin-A (IgA) rheumatoid factor (RF), and antikeratin antibodies (AKA) were performed. African Colombians with RA also were compared with Mestizo RA patients from Medellín, Colombia.. To determine the HI, all the outpatient charts for 1995 were reviewed (n = 3,044). PP during 1996 (Jan-Dec) was assessed by stratified sampling of all African Colombians aged 18 or more having arthralgia. Participants completed a survey and a pretested standard questionnaire, had hands and feet X-rays, and provided a blood sample. Total and IgA RF were measured by turbidimetry and ELISA, respectively; AKA were assessed by indirect immunofluorescence on rat esophagus. HLA-DRB1 and DQB1 alleles were determined by polymerase chain reaction technique with primers of specific sequence and by reverse dot blot.. The HI was 0.65 cases per 1,000 person years. There were 321 individuals with arthralgia (0.3%; 95% CI, 0.28-0.3), 18 of whom fulfilled the American College of Rheumatology criteria for RA (PP in the general population, 0.01%; 95% CI, 0.008-0.02). Lower erosion scores were seen in African Colombian patients compared to Mestizos (n = 56), although duration of disease was similar in each group. No association between any HLA allele and RA risk or RA severity or between autoantibodies and RA severity was observed in African Colombians. Comparisons showed no significant differences between African Colombians and Mestizo patients in the presence of RF (total and IgA), AKA, age at onset, extra-articular manifestations, formal education level, and history of malaria.. These results suggest that RA in African Colombian patients from Quibdo is rare, may be less severe in terms of radiographic damage than in Colombian Mestizo patients, and lacks association to HLA-DRB1 and DQB1 alleles. Additionally, RF (total and IgA) and AKA are not markers of progression and activity of the disease in this population.

Topics: Africa; Arthritis, Rheumatoid; Arthrography; Autoantibodies; Black People; Colombia; Female; Foot; Hand; HLA-DQ Antigens; HLA-DQ beta-Chains; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Immunoglobulin A; Indians, South American; Joints; Keratins; Male; Middle Aged; Prevalence; Rheumatoid Factor; Risk Factors

To investigate whether antikeratin antibodies (AKA) could be useful in the differential diagnosis of patients with rheumatoid arthritis (RA) compared to patients with hepatitis C virus (HCV) associated polyarthritis, who are seropositive for rheumatoid factor (RF).. AKA were assayed in 3 different groups of patients; all were RF seropositive: Group 1: 25 patients with HCV associated polyarthralgia or arthritis. Group 2: 33 patients with RA. Group 3: 13 patients with autoimmune disorders other than RA. Fifteen healthy individuals served as controls.. AKA were detected in 20/33 patients with RA (60.6%) compared to only 2/25 patients (8%) with HCV associated arthritis (p < 0.0001). AKA were observed in 2/13 patients of Group 3 (15.3%). These results were also statistically different from those of patients with RA (p = 0.008). AKA were not found in the sera of the healthy controls.. AKA is a useful marker to differentiate patients with RA from those with hepatitis C arthritis.

Topics: Adult; Aged; Antibodies; Arthritis; Arthritis, Rheumatoid; Autoimmune Diseases; Diagnosis, Differential; Female; Hepatitis C; Humans; Immunologic Tests; Keratins; Male; Middle Aged

To evaluate the clinical associations of antineutrophil cytoplasmic antibodies (ANCA) in patients with early rheumatoid arthritis (RA), as well as the possible predictive role of ANCA. We also assessed the overlap of ANCA with other specific serologic markers of RA.. Eighty-two RA patients with symptoms for < or = 12 months were studied for the presence of ANCA by immunofluorescence and specific enzyme immunoassays. ANCA were determined and clinical, radiographic, and laboratory data were collected at study entry and later at 12, 36, 60, and 84 months.. In 2 patients, the first serum samples (obtained at study entry) were no longer available for the determination of ANCA. Perinuclear ANCA (pANCA) were found in 40 patients (50%), and atypical cytoplasmic ANCA were found in 3 patients (4%) at study entry. Perinuclear ANCA-positive patients were significantly more frequently positive for rheumatoid factor (78%) than were ANCA-negative patients (54%) (P = 0.0297). Fifty-five percent of pANCA-positive patients and 22% of ANCA-negative patients were positive for antiperinuclear factor (P = 0.0044). Similarly, pANCA-positive patients had antikeratin antibodies more frequently than did ANCA-negative patients (35% versus 20%). During a 7-year followup, the progress of radiographic joint destruction, assessed with Larsen scores, was significantly more rapid in patients who were pANCA positive at study entry than in those who were ANCA negative (P = 0.0015). Also, the mean titer of pANCA at study entry was significantly higher in those patients who subsequently had advanced radiographic joint destruction at 60 and 84 months. The association of pANCA with rapid radiographic destruction in patients with early RA was further corroborated by a logistic regression analysis that selected pANCA positivity as an independent and statistically significant predictor of rapid radiographic joint destruction.. In patients with early RA, pANCA are associated with specific serologic markers of RA and predict rapid radiographic joint destruction.

Topics: Adolescent; Adult; Aged; Antibodies; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Antinuclear; Arthritis, Rheumatoid; Arthrography; Biomarkers; Disease Progression; Female; Follow-Up Studies; Humans; Keratins; Longitudinal Studies; Male; Middle Aged; Prognosis

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Biomarkers; Female; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Male; Middle Aged; Rheumatoid Factor; Sensitivity and Specificity

As the proportion of patients with rheumatoid arthritis (RA) who have anti-keratin antibodies (AKA) varies in different ethnic groups, we studied its occurrence in a hospital populations with RA and its association with different disease variables. Sera from 84 consecutive patients with RA, 100 healthy controls and 85 disease controls (polyarticular juvenile rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis) were tested for AKA by an indirect immunofluorescence assay that used rat esophagus as substrate. The proportion of patients with RA who had AKA (47/84) was higher than in healthy controls (2/100; P < 0.001) and in disease controls (2/85; P < 0.001). The frequency of AKA positivity was higher among patients who had severe disease (P < 0.05) and rheumatoid factor. Anti-keratin antibody is present in 56 per cent of our patients with RA and is associated with severe disease.

Topics: Adult; Arthritis, Rheumatoid; Autoantibodies; Female; Humans; Keratins; Male; Middle Aged

STATEMENT OF FINDINGS: An inception cohort of 238 patients having peripheral joint synovitis of less than 12 months duration was evaluated clinically and followed prospectively for 1 year to determine the clinical significance of a number of rheumatoid arthritis (RA) associated autoantibodies. Serum samples collected at the time of the initial evaluation were tested for rheumatoid factor (RF) and antibodies to Sa (anti-Sa), RA-33, (pro)filaggrin [antifilaggrin antibody (AFA)], cyclic citrullinated peptide (anti-CCP), calpastatin, and keratin [antikeratin antibody (AKA)]. RF had a sensitivity of 66% and a specificity of 87% for RA. Anti-Sa, AFA, and anti-CCP all had a specificity of more than 90%, but a sensitivity of less than 50% for this diagnosis. Overall, there was a high degree of correlation between AFA, AKA, anti-Sa or anti-CCP, this being highest between anti-Sa and anti-CCP (odds ratio, 13.3; P < 0.001). Of the 101 patients who were positive for at least one of these four autoantibodies, 57% were positive for only one. Finally, anti-SA identified a subset of predominantly male RA patients with severe, erosive disease. Anti-SA, AFA and anti-CCP are all specific for early RA but, overall, have little additional diagnostic value over RF alone. Although these antibodies may preferentially recognize citrullinated antigens, the modest degree of concordance between them in individual patient sera suggests that it is unlikely a single antigen is involved in generating these responses.

Topics: Acute Disease; Adult; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Calcium-Binding Proteins; Citrulline; Coenzyme A Ligases; Cohort Studies; Epitopes; Female; Filaggrin Proteins; Histocompatibility Testing; Humans; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Peptides, Cyclic; Predictive Value of Tests; Proteins; Rheumatoid Factor; Seroepidemiologic Studies; Synovitis

Topics: Animals; Antibodies; Antibodies, Antinuclear; Arthritis, Rheumatoid; Humans; Keratins; Rats

To assess the specificity and sensitivity of antiperinuclear factor (APF), anti-keratin antibody (AKA), anti-Sa antibody and anti-RA33 antibody in the diagnosis of RA.. 128 patients with RA, whose durations were within 1 year, were included. APF and AKA were detected by indirect immunofluorescence on the human buccal mucosa cells and the straum corneum of Wistar rat esophagus. Anti-Sa antibody and anti-RA33 antibody were examined by Western blotting. Sa antigen was extracted from human placenta while RA33 antigen from Ehrlich cells.. (1) The specificities and sensitivities of APF, AKA, anti-Sa antibody and anti-RA33 antibody were 91.4% (224/245) & 35.2% (45/128), 90.2% (221/245) & 32.0% (43/128), 90.6% (222/245) & 33.6% (43/128), 89.8% (220/245) & 28.9% (37/128), respectively, versus 72.3% (177/245) & 44.5% (57/128) for rheumatoid factor (RF). There were no statistical differences in the specificity between the four antibody groups and RF until 1:128 were taken as positive titer. Among 71 patients with RF-negative RA, 15 (21.1%) were positive for APF, 18 (25.4%) positive for AKA, 21 (29.6%) positive for anti-Sa antibody and 17 (23.9%) positive for anti-RA33 antibody. (2) Specificity and sensitivity were 95.1% (233/245) and 46.1% (59/128) respectively when two of the four antibodies turned out to be both positive. If three or more kinds were detected simultaneously, specificity was as much as 99.6% (108/128). (3) Statistical difference was found among the four groups defined by the number of positive antibodies in radiographic stage and patients assessment of illness.. (1) Dictation of APF, AKA, anti-Sa antibody and anti-RA33 antibody can greatly improve the specificity of diagnosis of early RA and serve as a complement when RF is negative. (2) Combined detection of the above four antibodies has a better discrimination ability as a laboratory criterion than that of RF. (3) Three or more positive antibodies may be an indicator of severe bone erosion and emergent demand for early treatment with better outcome.

Topics: Acute-Phase Proteins; Adult; Aged; Animals; Antibodies, Antinuclear; Antibody Specificity; Arthritis, Rheumatoid; Coenzyme A Ligases; Female; Humans; Keratins; Male; Middle Aged; Proteins; Rats; Rats, Wistar; Rheumatoid Factor; Serologic Tests

Presence of HLA-DR4, rheumatoid factor, and antikeratin antibody may predict severe rheumatoid arthritis.. To investigate potential associations between HLA DR4, rheumatoid factor and antikeratin antibody in rheumatoid arthritis patients.. Retrospective review of 169 patients followed at the Rangueil Teaching Hospital rheumatology department for rheumatoid arthritis.. No differences in prevalences of DR4 and DR1 were found between patients with and without rheumatoid factor or between patients with and without antikeratin antibody, suggesting that the production of rheumatoid factor and/or antikeratin antibody is not dependent on genetic factors. Substantial overlap was seen between rheumatoid factor and antikeratin antibody. All three parameters can be identified at first evaluation of a patient with joint disease.. It would be of interest to evaluate the cumulative predictive value of DR4 or DR1, rheumatoid factor and antikeratin antibody at disease onset.

Topics: Arthritis, Rheumatoid; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Histocompatibility Testing; HLA-DR1 Antigen; HLA-DR4 Antigen; Humans; Keratins; Male; Middle Aged; Retrospective Studies; Rheumatoid Factor

We evaluated the sensitivity and prognostic value of an enzyme-linked immunosorbent assay (ELISA) for the measurement of antifilaggrin antibodies (AFA), using filaggrin purified from human skin as an antigen. The AFA test was applied to a series of 306 patients with various recent-onset inflammatory joint diseases. The results were compared to those of the conventional immunofluorescence tests for antikeratin antibody (AKA) and antiperinuclear factor (APF) and of the rheumatoid factor (RF) tests from a previous study. There was a very good agreement between the results of the tests for APF and AFA (kappa-value 0.79 in patients with peripheral poly/oligoarthritis). The agreement between the tests for AKA and AFA was significant but less pronounced (kappa-value 0.50). The AFA test detected 10/22 of the RF-negative erosive cases, particularly those with a large number of erosive joints. Thus, the test for AFA supplements RF in the prediction of erosiveness.

Topics: Adult; Aged; Antibodies, Antinuclear; Arthritis, Rheumatoid; Enzyme-Linked Immunosorbent Assay; Epidermis; Filaggrin Proteins; Follow-Up Studies; Humans; Immunoglobulin G; Intermediate Filament Proteins; Keratins; Logistic Models; Middle Aged; Predictive Value of Tests; Prognosis; Rheumatoid Factor; Sensitivity and Specificity

Topics: Adult; Aged; Aging; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Female; Humans; Keratins; Male; Middle Aged; Seroepidemiologic Studies

It has been suggested that cytokeratin 19 is expressed in regenerated bronchoepithelial cells in patients with pulmonary fibrosis, and serum cytokeratin 19 fragment is elevated in patients with pulmonary fibrosis. We hypothesized that serum antibodies to cytokeratin 19 may be formed in patients with pulmonary fibrosis. To prove the existence of anti-cytokeratin 19 antibodies in patients' sera, human recombinant cytokeratin 19 was stained with patients' sera by a Western immunoblot. Then, we tried to establish an enzyme-linked immunosorbent assay to quantitate anti-cytokeratin 19 antibody in the sera of patients with idiopathic pulmonary fibrosis (IPF) and pulmonary fibrosis associated with collagen vascular disorders (PF-CVD). We demonstrated the anti-cytokeratin 19 antibody in patient' sera by a Western immunoblot. In patients with IPF and PF-CVD, significantly high anti-cytokeratin 19 antibody was demonstrated compared with normal volunteers, patients with chronic bronchitis, and patients with pneumonia. These results suggest that anti-cytokeratin 19 antibody may have played a role in the process of lung injury in pulmonary fibrosis.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoantibodies; Blotting, Western; Collagen Diseases; Dermatomyositis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Pulmonary Fibrosis; Sjogren's Syndrome

Only a few autoantibodies that are more or less specific for RA have been described so far. The rheumatoid factor most often tested for is not very specific for RA, while the more specific antiperinuclear factor for several reasons is not routinely used as a serological parameter. Here we show that autoantibodies reactive with synthetic peptides containing the unusual amino acid citrulline, a posttranslationally modified arginine residue, are specifically present in the sera of RA patients. Using several citrulline-containing peptide variants in ELISA, antibodies could be detected in 76% of RA sera with a specificity of 96%. Sera showed a remarkable variety in the reactivity pattern towards different citrulline-containing peptides. Affinity-purified antibodies were shown to be positive in the immunofluorescence-based antiperinuclear factor test, and in the so-called antikeratin antibody test, and were reactive towards filaggrin extracted from human epidermis. The specific nature of these antibodies and the presence of these antibodies early in disease, even before other disease manifestations occur, are indicative for a possible role of citrulline-containing epitopes in the pathogenesis of RA.

Topics: Amino Acid Sequence; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Citrulline; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratins; Molecular Sequence Data; Peptides

The majority of thymic lymphomas are either lymphoblastic lymphoma, large B cell lymphoma or Hodgkin's disease, and other types of non-Hodgkin lymphoma are rare. A case of low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) in the thymus is reported. A 55-year-old Japanese female with a history of rheumatoid arthritis (RA) complained of back pain. A mediastinal tumor was identified by computerized tomography and magnetic resonance imaging, and the thymus was resected through median sternotomy. The solid and nodular tumor had several small satellite extensions and was completely confined to within the thymus. Histologically, monotonous medium-sized centrocyte-like cells occupied the medulla of the thymus and infiltrated Hassall's corpuscles (lymphoepithelial lesions). Immunohistochemically, tumor cells were positive for CD20 and CD79a. IgA and kappa light chain restriction were also found in plasmacytoid cells in the tumor. Clonal rearrangement of the immunoglobulin heavy chain gene was demonstrated by polymerase chain reaction. This case was diagnosed as MALT-type low-grade B cell lymphoma in the thymus. This is the first report of low-grade B cell lymphoma in the thymus associated with RA. As autoimmune diseases are known to be associated with lymphoid neoplasms, it is suggested that the RA played an important role in the development of malignant lymphoma in this case.

Topics: Antigens, CD20; Arthritis, Rheumatoid; Biomarkers, Tumor; Blotting, Southern; Clone Cells; Female; Humans; Immunoglobulin Heavy Chains; Immunoglobulin kappa-Chains; Immunohistochemistry; Keratins; Lymphoma, B-Cell, Marginal Zone; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Thymus Neoplasms

Topics: Arthritis, Rheumatoid; Autoantibodies; Autoimmune Diseases; Biomarkers; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratins; Rheumatoid Factor

To determine the prevalence of antibodies to filaggrin in a cross sectional sample of patients with rheumatoid arthritis (RA).. Filaggrin from human skin was either extracted with 0.05% Nonidet P-40 and then partially purified by precipitating in ethanol and resuspending in water (Nonidet preparation) or extracted with 9 M urea and then purified by sequential fractionation on a DEAE Sephadex column and on a strong cation exchange column (purified preparation). Antibodies to filaggrin were detected using immunoblotting techniques with sera diluted 1:50. Antikeratin antibodies (AKA) were detected using indirect immunofluorescence microscopy on sections of rat esophagus.. Antibodies to filaggrin were detected in 5 of 30 sera of patients with RA using filaggrin from the Nonidet preparation and 6 of 49 sera using filaggrin from the purified preparation. AKA were detected in 13 of 40 sera. A positive correlation existed between the presence of AKA and the presence of antibodies to filaggrin using the purified preparation (p=0.017).. These data indicate that the reactivity of RA sera with filaggrin is not identical to the presence of AKA and is variable depending upon the preparation of filaggrin used. The diagnostic value of antibodies to filaggrin remains to be proven.

Topics: Animals; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Biomarkers; Epidermis; Filaggrin Proteins; Humans; Immunoblotting; Intermediate Filament Proteins; Keratins; Rats

We previously reported that so-called antikeratin antibodies (AKA) and antiperinuclear factor (APF) recognize epitope(s) present on human epidermal filaggrin. In the present study, we developed a new diagnostic test for rheumatoid arthritis (RA) based on detection of antifilaggrin autoantibodies (AFA) by immunoblotting.. We tested 670 serum samples, including 190 RA. AFA titers were estimated by immunoblotting on filaggrin enriched human epidermis extracts, and AKA titers by indirect immunofluorescence (IIF) on rat esophagus epithelium. Diagnostic values of the tests were compared.. Each test resulted in diagnosis of more than 40% of RA samples, with a specificity of 0.99. Although the tests were strongly correlated, their association allowed the diagnosis of more than 60% of RA samples, with the same specificity.. Immunoblot detection of AFA, a simple and standardizable test, may be an alternative or complement to conventional IIF detection of AKA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Arthritis, Rheumatoid; Autoantibodies; Epidermis; Epithelium; Esophagus; Female; Filaggrin Proteins; Fluorescent Antibody Technique, Indirect; Humans; Immunoblotting; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Rats

The purpose of this study was to examine the relationship between circulating antibodies to stratum corneum (AKA) and antiperinuclear factors (APF) on one hand, and the x-ray progression of joint damage in chronic poly/oligoarthritis on the other hand. The analysis involved 133 patients with either rheumatoid or nonspecific arthritis derived from a cohort of 442 patients with recent onset arthritis. The patients were followed up for eight years with regular clinical, laboratory, and radiological evaluations. Radiographic evidence of joint destruction was quantitated by a radiographic index based on the Larsen grading. AKA and APF were detected, either at entry or at follow-up, in 26 and 54 patients, respectively. Seventy-six of the 133 patients had developed erosions. All AKA-positive patients had a rheumatoid factor-positive erosive poly-arthritis. The presence of APF was also associated with a progressive arthritis although four APF-positive patients had a non-erosive disease. Neither AKA nor APF were able to distinguish a particularly severe form of progressive RA.

Topics: Adolescent; Adult; Ankle Joint; Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Cohort Studies; Disease Progression; Hand; Humans; Keratins; Radiography; Rheumatoid Factor; Skin; Tarsal Joints; Wrist Joint

Autoantibodies such as rheumatoid factor (RF), antikeratin antibodies (AKA), antiperinuclear factor (APF), and anti-RA 33 antibodies are considered of value for the diagnosis of RA. The purpose of this study was to evaluate these autoantibodies as predictors of severe radiographic damage in rheumatoid arthritis (RA).. Eighty six patients with RA (70 women, 16 men) fulfilling 1987 ACR criteria were selected from a cohort of 469 patients followed up since the first year of RA onset because they could be divided in two groups according to the severity of the radiographic damage. These 86 patients had a mean (SD) disease duration of eight (four) years: 43 patients had severe radiographic damage (Larsen score > or = 2) and 43 had limited radiographic damage (Larsen score < 2). The two groups were matched by disease duration and sex. The following autoantibodies were looked for: RF, ANA, AKA, APF, and anti-RA 33 antibodies. In addition, HLA class II DR beta alleles and standard inflammatory parameters (erythrocyte sedimentation rate, C reactive protein) were determined.. Patients with severe radiographic damage differed from those with limited radiographic damage in that they had higher RF (p = 0.01), APF (p < 0.02), and AKA (p = 0.001) titres. Stepwise regression analysis was done to calculate the odds ratios (OR) for each clinical and laboratory variable; only presence of cutaneous nodules (OR: 14.9; 95% CI: 7, 128), HLA DRB1*04 or DRB1*01 (OR: 7.53; 95% CI: 1.32, 42.9), AKA (OR: 3.11; 95%, CI: 0.58, 16.8), a high erythrocyte sedimentation rate (OR: 2.66; 95% CI: 0.60, 11.9), and a high C reactive protein value (OR: 7.4; 95% CI: 1.43, 38.1) were predictive of severe radiographic damage.. These data suggest that the risk of severe radiographic damage in RA patients is higher when cutaneous nodules, HLA DRB1*04 or DRB1*01, and/or AKA are present. The other autoantibodies of diagnostic significance are of little help for predicting joint destruction.

Topics: Adolescent; Adult; Aged; Antibodies, Antinuclear; Arthritis, Rheumatoid; Arthrography; Autoantibodies; Biomarkers; Blood Sedimentation; C-Reactive Protein; Evaluation Studies as Topic; Female; Foot; Hand; HLA-DR Antigens; HLA-DRB1 Chains; Humans; Keratins; Male; Middle Aged; Odds Ratio; Prognosis; Rheumatoid Factor; Wrist Joint

The goal of this prospective longitudinal study was to determine the serological profile of early rheumatoid arthritis (RA), and to test whether antikeratin antibody (AKA), antiperinuclear factor (APF), anti-RA33 antibody and antinuclear antibodies (ANA) had an additional diagnostic value when prescribed after rheumatoid factor (RF)-detecting methods. Sixty-nine patients with early polyarthritis suggestive of RA, seen between 1991 and 1993, were included. Five autoantibodies (i.e. RF, AKA, APF, RA33, ANA) were looked for at regular intervals. After 24 months follow-up, patients were classified as having RA (n = 49), unclassified polyarthritis (UP; n = 15) or other rheumatic diseases. Among patients with early RA, the sensitivity of these markers was 40.8% for RF, 36.7% for AKA, 28.6% for APF and 28.6% for anti-RA33. Among RF-negative RA patients, 51.7% were positive for AKA, APF, anti-RA33 antibodies and/or ANA. Positivity of the three recent markers usually persisted throughout follow-up, whereas RF was lost by 58% of patients with early, RF-positive, treated RA. Using multivariate analysis, only latex, RF test and AKA or APF had an independent and statistically significant diagnostic value for early RA. Our data suggest that RF and AKA (or APF) should be concomitantly determined for diagnosis in patients with suspected early RA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibodies, Antinuclear; Arthritis; Arthritis, Rheumatoid; Autoantibodies; Female; Follow-Up Studies; Humans; Immunologic Tests; Keratins; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Rheumatoid Factor; Sensitivity and Specificity

Topics: Adult; Aged; Antibodies, Antinuclear; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Female; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Liver Cirrhosis, Biliary; Male; Middle Aged; Prognosis

Since they were first described, serum IgG antibodies to the stratum corneum of rat oesophagus epithelium, highly specific for rheumatoid arthritis (RA), have been consensually called antikeratin antibodies (AKA). However, we recently demonstrated that they actually recognize three new proteins of rat oesophagus epithelium distinct from cytokeratins, and also human epidermal filaggrin. In this work we provided further evidence that AKA and RA-associated anti-filaggrin autoantibodies are the same antibodies. Moreover, analysing by indirect immunofluorescence on human skin a large series of 212 well characterized RA sera and anti-filaggrin autoantibodies purified from RA sera by affinity chromatography, we demonstrated the specific binding of AKA to the stratum corneum of human epidermis and the absence of any staining of the granular keratinocytes. This binding was confirmed and the AKA antigen precisely localized in human epidermis by immunoelectron microscopy. The antigen was found to be restricted to the filaggrin-containing intracellular fibrous matrix of the corneocytes, up to the desquamating cells. In contrast, MoAbs directed to human filaggrin and to profilaggrin, its precursor, not only stained the intracellular matrix of the lower corneocytes but also the keratohyalin granules of the granular cells, where profilaggrin is stored. These results reinforced by the absence of immunoblotting reactivity of RA sera to profilaggrin suggest that the epitopes recognized by AKA are absent from profilaggrin. Their identification may provide more insight into the pathogenesis of RA.

Topics: Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Blotting, Western; Epidermis; Female; Filaggrin Proteins; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Immunohistochemistry; Intermediate Filament Proteins; Keratins; Male; Middle Aged; Protein Precursors

The so-called antikeratin antibodies (AKA) and the antiperinuclear factor (APF) are the most specific serological markers of RA. Using indirect immunofluorescence, AKA label the stratum corneum of various cornified epithelia and APF the keratohyalin granules of human buccal mucosa epithelium. We recently demonstrated that AKA recognize human epidermal filaggrin. Here, we report the identification of the major APF antigen as a diffuse protein band of 200-400 kD. This protein is seen to be closely related to human epidermal (pro) filaggrin since it was recognized by four antifilaggrin mAbs specific for different epitopes, and since the APF titers of RA sera were found to be correlated to their AKA titers and to their immunoblotting reactivities to filaggrin. Immunoabsorption of RA sera on purified epidermal filaggrin abolished their reactivities to the granules of buccal epithelial cells and to the 200-400-kD antigen. Moreover, antifilaggrin autoantibodies, i.e., AKA, affinity purified from RA sera, were shown to immunodetect the 200-400-kD antigen and to stain these granules. These results indicate that AKA and APF are largely the same autoantibodies. They recognize human epidermal filaggrin and (pro) filaggrin-related proteins of buccal epithelial cells. Identification of the epitopes recognized by these autoantibodies, which we propose to name antifilaggrin autoantibodies, will certainly open new paths of research into the pathophysiology of RA.

Topics: Antibodies, Antinuclear; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Biomarkers; Blotting, Western; Filaggrin Proteins; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Molecular Weight; Mouth Mucosa

To evaluate the usefulness for the diagnosis of rheumatoid arthritis of tests for rheumatoid factors, antiperinuclear factors, antikeratin antibodies, and the HLA DR4 antigen, we retrospectively reviewed the medical records of 138 patients consecutively admitted to our rheumatology department between January 1, 1988 and December 31, 1990 for evaluation of peripheral inflammatory joint manifestations. Each patient had a standard work-up including a physical examination, laboratory tests, and roentgenograms. In 1994, after a follow-up of three to six years, the final diagnosis was rheumatoid arthritis in 39 patients and another well-defined disorder in 63; no diagnosis was established in 36 patients, among whom nine were lost to follow-up. The decreasing order of diagnostic usefulness was antiperinuclear factors, HLA DR4, rheumatoid factors (latex test), and antikeratin antibody. The likelihood of rheumatoid arthritis was greatest in those patients with positivity of two of the three following markers: rheumatoid factors, antiperinuclear factors, and the HLA DR4 antigen.

Topics: Adult; Aged; Aged, 80 and over; Antibodies; Antibodies, Antinuclear; Arthritis, Rheumatoid; Evaluation Studies as Topic; Female; HLA-DR4 Antigen; Humans; Keratins; Male; Middle Aged; Predictive Value of Tests; Retrospective Studies; Rheumatoid Factor; Sensitivity and Specificity

Sera from 107 patients with rheumatoid arthritis (RA), 120 patients with other rheumatic diseases and 60 blood donors were tested with indrect immunofluorescence on the middle third of Wistar rat oesophagus as a substrate for the presence of antikeratin antibodies (AKA). By labelling the stratum corneum and stratum spinosum with IgG antibodies, three patterns of reaction were distinguished. Among them, only one pattern which showed an intense linear laminated fluorescence on stratum corneum and a weak fluorensence on stratum spinosum was valuable for the diagnosis of RA, with a specificity of 99% and a sensitivity of 23%. It was also found that they were not related to the presence of rheumatoid factor or anti-RA 33,000/36,000 antibodies. Thus, AKA might be another marker antibody in RA.

Topics: Animals; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Fluorescent Antibody Technique, Indirect; Humans; Keratins; Rats; Rats, Wistar; Sensitivity and Specificity

The presence of antikeratin antibodies (AKA) has been associated with rheumatoid arthritis (RA) in patients from north and central Europe. Our aim was to investigate the prevalence of AKA in Greek patients with RA.. One hundred and twenty two sera of Greek patients with RA were tested for the presence of AKA by an indirect immunofluorescence technique, and HLA-DR typing was performed by restriction fragment length polymorphism.. Nineteen of 122 (16%) Greek patients with RA were positive for AKA. The percentage of AKA in Greek patients with RA is lower than described previously. These antibodies correlated with a male preponderance (p < 0.01) and were associated with the presence of rheumatoid factor (RF) (p < 0.05) and with HLA-DR1 antigen (p < 0.05).. Our results suggest that AKA are present frequently in Greek patients with RA. Their presence was found to be associated with RF and HLA-DR1 antigen. This emphasizes the different clinical expression of RA in Greece.

Topics: Adult; Aged; Antibodies; Arthritis, Rheumatoid; Female; Fluorescent Antibody Technique, Indirect; Greece; HLA-DR1 Antigen; Humans; Keratins; Male; Middle Aged

We report the isolation and characterization of a 65,000 MW chondrocyte autoantigen (CH65) which may be involved in rheumatoid arthritis. This chondrocyte-specific antigen reacted with sera from patients with rheumatoid arthritis (RA). CH65 did not cross-react with a polyclonal antibody raised against microbial heat-shock protein (hsp) 65, anti-human hsp 65 monoclonal antibodies (mAb) (LK1 and LK2), anti-microbial hsp 65 mAb (IA10, IIC8 and WTB-78H1) and anti-cytokeratin 8, 18, 19 mAb (NCL5D3MAb). CH65 could be purified from chicken chondrocyte membranes by ammonium sulphate precipitation and a novel electro-gel-filtration method. The amino acid analysis yielded an unusually high degree of glycine, serine and asparagine residues. The internal amino acid sequence obtained by tryptic digestion revealed homologies with the cytokeratin family. Despite these homologies, CH65 lacked immunological cross-reactivity with commercial anti-cytokeratin antibodies. Mice mAb generated against the purified CH65 (C6) were used to identify the protein as a tissue-specific constitutive protein membrane from chondrocytes. Sera from patients with RA cross-reacted with purified CH65. The stress or heat-shock protein (hsp 65), implicated in the development of experimental and clinical arthritis, showed no immunological cross-reactivity with CH65 in Western blots. These findings suggest that CH65 may represent an interesting cartilage-specific new antigen in RA. The availability of this antigen in purified form and specific mAb may offer useful tools in arthritis research.

Topics: Amino Acids; Animals; Arthritis, Rheumatoid; Autoantigens; Blotting, Western; Cartilage; Chickens; Electrophoresis, Polyacrylamide Gel; Heat-Shock Proteins; Keratins

Topics: Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Biomarkers; Finland; Humans; Keratins; Moscow; Prognosis; Rheumatoid Factor

To assess the diagnostic value for rheumatoid arthritis (RA), of an immunoblotting assay based on the rat oesophagus epithelium antigens recognised by the so-called 'antikeratin antibodies' ('AKA'), antigens that have been identified as three non-cytokeratin proteins (referred to as A, B and C proteins).. After polyacrylamide gel electrophoresis in non-denaturing conditions and electrotransfer of an epithelial extract, the immunoreactivities to the A, B and C proteins of a series of serum samples from 88 patients with RA and 100 patients with non-rheumatoid rheumatic diseases, were semiquantitatively evaluated.. A total of 81.8% of RA serum samples recognised the three proteins, while 91% of non-RA serum samples only weakly recognised the A and B proteins but not the C protein. Only in the group of RA patients, were the titres of the antibodies to the A, B and C proteins found to be significantly correlated with each other and with the titres of 'AKA' detected by the standard indirect immunofluorescence (IIF) method. For a diagnostic specificity of 99%, the diagnostic sensitivities of the detection of the A and B proteins were 50% and 43.2%, respectively, when those of the detection of 'AKA' by IIF and of IgM-rheumatoid factor by enzyme-linked immunosorbent assay were 42% and 54%, respectively. In contrast, at a same specificity of 99%, the diagnostic sensitivity of the detection of the C protein was significantly higher with a value of 70.5%.. This immunoblotting assay which is the first immunochemical method proposed for the detection of 'AKA, should be validated on larger series of patients but can already be considered as a very powerful test for the serological diagnosis of RA.

Topics: Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Electrophoresis, Polyacrylamide Gel; Epithelium; Esophagus; Humans; Immunoblotting; Keratins; Rheumatoid Factor; Sensitivity and Specificity

An attempt was made to characterise the antigens recognised by serum IgG antibodies directed to the stratum corneum of rat oesophagus epithelium, the so-called 'antikeratin antibodies', which were shown to be highly specific for rheumatoid arthritis (RA) and thus to have an actual diagnostic value.. Immunoblotting was performed with RA serum samples on different extracts of rat oesophagus epithelium separated by various monodimensional and two dimensional electrophoreses.. Three low-salt-soluble antigens sensitive to proteinase K and, therefore, of protein nature were identified. Two proteins, with apparent molecular masses of 210 and 120-90 kilodaltons, shared isoelectric points ranging from 5.8 to 8.5; the third protein exhibited isoelectric points from 4.5 to 7.2 while its molecular mass ranged from 130 to 60 kilodaltons. Immunoadsorption of RA serum samples onto cytokeratins extracted from the stratum corneum of rat oesophagus epithelium did not change their immunoreactivity towards the three antigenic proteins. Widely used deglycosylation and dephosphorylation methods failed to modify either the electrophoretic migration of the proteins or their immunoreactivity with RA serum samples.. The so-called 'antikeratin antibodies' do not react with cytokeratins. They specifically recognise three late epithelial differentiation proteins which had not been previously described. These proteins may be related to (pro)filaggrin.

Topics: Animals; Antibodies; Antigens; Arthritis, Rheumatoid; Endopeptidases; Epithelium; Epitopes; Esophagus; Filaggrin Proteins; Humans; Immunoblotting; Immunoglobulin G; Isoelectric Point; Keratins; Male; Rats; Rats, Wistar

The aim of the study was to establish the benefit of an additional hypothetical laboratory criterion for rheumatoid arthritis (RA), comprising positivity for antikeratin antibody (AKA) and/or antiperinuclear factor (APF). The tests were applied to a series of 308 hospital patients with various recent-onset inflammatory joint diseases who were followed for 3 years. The performance of APF and AKA was compared with rheumatoid factor (RF). The most sensitive (.72) but the least specific (.86) test for RA was the latex test. The most specific (.96) but the least sensitive (.33) test was AKA. Waaler-Rose and APF were intermediate. AKA and/or APF positive patients had significantly more erosions than patients negative for these autoantibodies. Despite the impressive performance characteristics of APF and AKA, the actual classification impact achieved, as compared to using RF as the sole laboratory criterion, turned out to be moderate. This is because the criteria proved to be interrelated. Unlike RF, AKA and APF are not suited to the general laboratory, at least not in their present form. Moreover they so far lack the broad data base of RF.

Topics: Antibodies; Antibodies, Antinuclear; Arthritis, Rheumatoid; Humans; Immunologic Tests; Keratins; Rheumatoid Factor; Sensitivity and Specificity

Topics: Arthritis, Rheumatoid; Autoantibodies; Cell Nucleus; Enzyme-Linked Immunosorbent Assay; Humans; Intermediate Filament Proteins; Keratins; Lamins; Nuclear Proteins

To investigate whether levels of antibodies to cytokeratin-18 (CK-18) and epidermal keratin (EPK) were raised in patients with rheumatoid arthritis (RA).. We measured antibodies to CK-18 and EPK in patients with RA and in patients with osteoarthritis (OA), as well as in normal control subjects by means of an enzyme-linked immunosorbent assay.. IgA antibodies to both CK-18 and EPK were significantly increased in patients with RA compared with the controls and with patients with OA (P < 0.0001). No difference was noted in the levels of IgG or IgM antibodies to CK-18 or EPK between controls and patients with OA or RA.. Raised levels of IgA autoantibody to CK-18 and EPK may reflect damage to cytokeratin-containing cells (e.g., in synovial endothelium) and could be a useful disease marker in RA.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Autoantibodies; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin A; Immunoglobulin M; Keratins; Male; Middle Aged; Reference Values; Skin

The authors phenotypically compared epithelial and nonepithelial components of human corneal and conjunctival microenvironments using a panel of monoclonal antibody reagents that included markers of epithelial cell maturation, markers of mesodermal-derived fibrous tissue and vessels, markers of specific keratins, and markers of major histocompatibility complex Class I and II antigens.. Corneoscleral rims obtained after trephination of the donor button for use in penetrating keratoplasty procedures were studied.. A comparison of cornea and conjunctiva with anti-epithelial and antikeratin antibodies demonstrated that corneal and conjunctival keratinocytes undergo similar antigenically defined pathways of maturation. However, the reactivity of antibody 12/1-2 (antibody against low molecular weight keratins) with conjunctival but not corneal basal cells suggested differences in keratin expression between the two epithelial types. Using antibodies against major histocompatibility complex Class I and II antigens, it was demonstrated the two tissues were similar with Class I determinants found on all epithelial, stromal, and endothelial cells, and Class II determinants found on Langerhans' cells, vessels, and a subset of stromal cells.. The availability of tissue-specific markers of epithelial and nonepithelial components of the cornea and conjunctiva should be of use in the study of the roles the ocular microenvironment might play in the pathogenesis of ocular inflammatory diseases.

Topics: Animals; Antibodies, Monoclonal; Arthritis, Rheumatoid; Cell Division; Conjunctiva; Cornea; Corneal Diseases; Epithelium; Fluorescent Antibody Technique; Histocompatibility Antigens Class I; Histocompatibility Antigens Class II; Humans; Immunophenotyping; Keratins; Keratoplasty, Penetrating; Mice; Skin

In rheumatoid arthritis (RA), the high diagnostic value of serum antibodies to the stratum corneum of rat esophagus epithelium has been widely reported. These so-called "antikeratin antibodies," detected by indirect immunofluorescence, were found to be autoantibodies since they also labeled human epidermis. Despite their name, the actual target of these autoantibodies was not known. In this study, a 40-kD protein (designated as 40K), extracted from human epidermis and specifically immunodetected by 75% of RA sera, was purified and identified as a neutral/acidic isoform of basic filaggrin, a cytokeratin filament-aggregating protein, by peptide mapping studies and by the following evidences: (a) mAbs specific for filaggrin reacted with the 40K protein; (b) the autoantibodies, affinity-purified from RA sera on the 40K protein, immunodetected purified filaggrin; (c) the reactivity of RA sera to the 40K protein was abolished after immunoadsorption with purified filaggrin; (d) the 40K protein and filaggrin had similar amino acid compositions. Furthermore, autoantibodies against the 40K protein and the so-called "antikeratin antibodies" were shown, by immunoadsorption experiments, to be largely the same. The identification of filaggrin as a RA-specific autoantigen could contribute to the understanding of the pathogenesis of this disease and, ultimately, to the development of methods for preventing the autoimmune response.

Topics: Amino Acids; Animals; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Electrophoresis, Gel, Two-Dimensional; Filaggrin Proteins; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Molecular Weight; Rats

Antikeratin antibody (AKA) and antiperinuclear factor (APF) are antibodies characteristic for rheumatoid arthritis (RA). Our purpose was to obtain information on the occurrence of APF before the onset of clinical disease and on the occurrence of AKA and APF in cases with false-positive rheumatoid factor (RF) reactions.. AKA and APF were measured with indirect immunofluorescence technique using rat esophagus and buccal mucosa cells, respectively, as antigen source.. Five of 30 preillness specimens from subjects who later developed seropositive RA were positive for AKA and APF, 3 sera were positive for only AKA and 3 for only APF. All the eleven sera positive for AKA or APF were RF positive. Both AKA and APF were detected in 6 of 70 sera from RF positive subjects who did not develop RA within a 10-year followup, 3 sera were positive for only AKA and 3 for only APF.. AKA and APF appear to be linked markers of an immunological process which, in RF positive subjects, predicts the development of clinical arthritis. However, disease manifestations develop in only a proportion of cases.

Topics: Adult; Antibodies; Antibodies, Antinuclear; Arthritis, Rheumatoid; Biomarkers; Cohort Studies; Female; Humans; Keratins; Male; Predictive Value of Tests; Rheumatoid Factor

Topics: Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Humans; Keratins; Predictive Value of Tests

Antibodies to the stratum corneum of rat oesophagus (antikeratin antibodies) were assayed by indirect immunofluorescence in a prospective study of patients with early rheumatoid arthritis (RA). At the beginning of the study, antikeratin antibodies of IgG class were detected in serum samples from 27/71 (38%) patients compared with 1/20 (5%) control patients with reactive arthritis, and 1/38 (3%) healthy blood donors. At the end of the two year follow up, 27/67 (40%) patients with RA were positive for antikeratin antibodies. The patients with RA who were initially positive for antikeratin antibodies had a more active disease course than the patients negative for antikeratin antibodies as measured by clinical, laboratory, and radiological variables. The prevalence of positivity for antikeratin antibodies fluctuated during the follow up, the variation paralleling the disease activity. The occurrence of HLA-DR4 was similar in patients with RA who were positive and negative for antikeratin antibodies. Antikeratin antibodies were also found in seronegative patients with RA, confirming that antikeratin antibodies do not have rheumatoid factor activity. These results show that antikeratin antibodies are detectable at the time of the initial diagnosis of RA and that the positivity for antikeratin antibodies may have prognostic significance in early RA.

Topics: Adult; Aged; Antibodies; Arthritis, Rheumatoid; Biomarkers; Female; Fluorescent Antibody Technique; HLA-DR4 Antigen; Humans; Keratins; Male; Middle Aged; Prognosis; Prospective Studies

We sought to determine whether circulating antikeratin antibodies (AKA) precede the onset of rheumatoid arthritis (RA).. By matching the registers of 2 previous population studies with the registry of patients receiving antirheumatic drugs several years later, pre-illness serum specimens could be obtained from 39 individuals who subsequently developed RA. AKA were assayed with the standard indirect immunofluorescence technique.. Ten of 39 serum specimens from individuals who subsequently developed seropositive RA, and 1 of 15 sera from individuals who developed seronegative RA, were positive for IgG-class AKA by immunofluorescence assay. The AKA-positive sera were also positive for rheumatoid factors.. The findings focus attention on the role of pre-illness immunologic events in the pathogenesis of RA.

Topics: Antibodies; Arthritis, Rheumatoid; Fluorescent Antibody Technique; Humans; Keratins

In order to study the relationships between the circulating IgG autoantibodies to epidermal cytokeratins (AECK), which were described in normal human sera as well as in sera from patients with various diseases, and the so-called 'antikeratin' IgG antibodies ('AKA'), which are highly specific for rheumatoid arthritis (RA), we simultaneously investigated AECK by a specific ELISA using cytokeratins from human stratum corneum (SC) and 'AKA' by semiquantitative indirect immunofluorescence assay on rat oesophagus epithelium, in a large series of 595 rheumatic sera including 229 RA. AECK were found to be present in all the 595 sera, with large inter-individual variations in titre. Whatever the titre chosen as threshold, the autoantibodies (auto-Ab) were never found to be specific for any rheumatic disease. Moreover, in RA, they were found to vary independently of IgM rheumatoid factor (IgM-RF), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), while they were found to vary in parallel with the total serum IgG concentration. In contrast, although 568 of the 595 rheumatic sera contained antibodies that labelled the rat oesophagus SC, the highest titre-like values were obtained with RA sera. At a convenient threshold, 95 (41.5%) of the 229 RA were detected while only three false positives (0.08%) remained among the 366 non-RA sera. Moreover, in RA, 'AKA' were found to be related to IgM-RF, ESR and CRP, while their titre was found to be independent of the total serum IgG concentration. Lastly, no statistical correlation was found between the antibodies, either in the whole sample of 595 sera or in any diagnostic group. In conclusion, the simultaneous investigation of AECK and 'AKA' showed that they differ from each other in all the aspects explored. AECK belong to the widely explored family of natural auto-Ab against cytoskeleton components and do not constitute a diagnostic marker while, on the other hand, 'AKA' confirmed their high diagnostic specificity for RA. It can also be asserted that, in spite of their name, 'AKA' do not recognize human epidermal cytokeratins, at least in the denatured form they present in ELISA. Therefore, they recognize either conformational epitope(s) appearing on cytokeratins during the late stages of the cornification process, or epitope(s) borne by rat cytokeratins but absent on human cytokeratins, or lastly a non-cytokeratin SC antigen.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Epithelium; Esophagus; Female; Humans; Immunity, Innate; Immunoglobulin G; Keratins; Male; Middle Aged; Rheumatic Diseases; Skin

The antiperinuclear factor, an autoantibody specific for rheumatoid arthritis, was found in 51/63 (81%) patients with rheumatoid arthritis by indirect immunofluorescence on human buccal mucosa cells. The sensitivity of the antiperinuclear factor test was increased by pretreating the buccal mucosa cells with 0.5% Triton-X100. The specificity of the test for rheumatoid arthritis as compared with control serum samples was maintained. The localisation of the perinuclear factor in the keratohyalin granules of the buccal mucosa cells was verified by immunoelectron microscopy. The perinuclear factor was found to be an insoluble protein whose antigenicity was sensitive to various fixation procedures. In serum samples from patients with rheumatoid arthritis there was a positive correlation between the presence of antiperinuclear factor and the presence of the so called antikeratin antibodies as detected by immunofluorescence on unfixed rat oesophagus cryostat sections. No relation was found between the presence of the perinuclear factor and either the rheumatoid factor, Epstein-Barr virus components, or any cytokeratin. By double immunofluorescence an exact colocalisation of the perinuclear factor and profilaggrin was found. Although the precise biochemical identity of the perinuclear factor remains unclear, our results suggest that it is a protein only present in the fully differentiated squamous epithelial cell layer.

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Filaggrin Proteins; Fluorescent Antibody Technique; Humans; Intermediate Filament Proteins; Keratins; Microscopy, Immunoelectron; Mouth Mucosa; Nuclear Proteins; Phosphoproteins; Protein Precursors; Sensitivity and Specificity

P62 is a synthetic peptide which corresponds to the glycine/alanine repeat sequence of Epstein-Barr virus nuclear antigen-1. It is the main epitope recognised by anti-rheumatoid arthritis nuclear antigen antibodies. It was shown previously that anti-P62 antibodies were raised fourfold in patients with rheumatoid arthritis compared with controls. To examine the possibility that this increase was due to cross reactive autoantibodies binding to P62, anti-P62 antibodies from serum samples taken from 10 patients with rheumatoid arthritis and five healthy controls were purified by affinity chromatography. Immunoglobulin G anti-P62 antibodies purified from four of 10 serum samples from patients with rheumatoid arthritis also reacted with human epidermal keratin, denatured collagen type II and actin, but not with influenza antigens, as determined by enzyme linked immunosorbent assay (ELISA). Anti-P62 antibodies in serum samples from healthy controls and patients with rheumatoid arthritis reacted with epidermal keratin by immunoblotting. It is suggested that antibodies to the glycine/alanine repeat sequence of Epstein-Barr nuclear antigen-1 recognise homologous epitopes on keratin, actin, and collagen. It is also possible that molecular mimicry between a major epitope on the Epstein-Barr virus and several autoantigens might contribute to the breakdown of tolerance and autoimmunity in patients with rheumatoid arthritis.

Topics: Actins; Alanine; Amino Acid Sequence; Antibodies, Viral; Antigens, Viral; Arthritis, Rheumatoid; Autoantigens; Collagen; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Epstein-Barr Virus Nuclear Antigens; Glycine; Herpesvirus 4, Human; Humans; Immunoblotting; Keratins; Molecular Sequence Data; Peptides

An unusually heavy load of Epstein-Barr virus (EBV) infection and autoimmunity to collagen are believed to be contributing factors to the pathogenesis of rheumatoid arthritis (RA). The present report presents data showing that p107, the major epitope of the EBV-encoded EBNA-1 antigen, cross-reacts with denatured collagen (DC) and keratin (K), suggesting a new likely link among RA, EBV-1, and these autoantigens. A radioimmunoassay using antigen-coated microtiter plates was used to demonstrate antibodies in sera of patients with RA and sera of healthy donors against p107, DC, and K. Specificity of the antibodies was ascertained by inhibition tests with the homologous antigens. Cross-reactivity among anti-p107, anti-DC, and anti-K antibodies was assayed by the ability of a given antigen to block the binding of nonpurified or affinity-purified antibodies to plates coated with another antigen. Most of the sera contained antibodies to all three antigens, but only anti-DC antibodies were present in higher titers in RA sera. Preincubation of sera with p107 appreciably reduced their binding to plates coated with DC or K. On the other hand, preincubation with DC (in solution or bound to Sepharose) did not result in consistent reduction of anti-p107 titers. Tests with affinity-purified antibodies revealed the existence of two antibodies populations, one of which reacted preferentially with p107, the other with DC. The cross-reactivity of the anti-p107 antibodies with DC and K suggests that such antibodies, produced by RA patients following persistent stimulation with EBV, might react in vivo with collagen (and keratin) exposed in previously damaged areas and thus reinforce the disease process.

Topics: Adult; Aged; Antigens, Viral; Arthritis, Rheumatoid; Collagen; Cross Reactions; Epstein-Barr Virus Nuclear Antigens; Female; Herpesvirus 4, Human; Humans; Keratins; Male; Middle Aged

Antibodies to recombinant heterogeneous nuclear RNP core protein A1 were detected in sera from 27 of 58 patients with rheumatoid arthritis (RA) and from 7 of 31 patients with systemic lupus erythematosus, by immunoblotting and enzyme-linked immunosorbent assay. Protein A1 consists of 2 distinct domains: The N-terminal sequence is identical to a single-stranded DNA binding protein termed UP1, and the C-terminal domain shows a partial homology with keratin. All 7 A1-positive systemic lupus erythematosus sera reacted with UP1, whereas 9 of the 27 A1-positive RA sera did not. In RA, anti-A1 activity was significantly associated with antikeratin antibodies (AKA); these antibodies were present in 23 of 27 A1-positive sera and 10 of 31 A1-negative sera (P less than 0.01). Immunoabsorption with recombinant protein A1 resulted in a significant reduction of AKA titers in 6 of 10 RA sera tested, suggesting that AKA from RA patients may cross-react with the C-terminal portion of the heterogeneous nuclear RNP protein A1.

Topics: Adolescent; Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Autoantigens; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Humans; Immunoblotting; Keratins; Lupus Erythematosus, Systemic; Male; Middle Aged; Nuclear Proteins; Recombinant Proteins; snRNP Core Proteins; Viral Core Proteins

Serum IgG, labelling the stratum corneum of the rat oesophagus epithelium, so-called anti-keratin antibodies (AKA) constitute the most specific marker for the diagnosis of rheumatoid arthritis. In this study, we investigated 31 IgG AKA-positive rheumatoid sera and 21 control sera from patients with non-rheumatoid inflammatory rheumatic diseases. The serum level of IgG1,2,3 and 4 was determined by radial immunodiffusion and the subclass distribution of IgG AKA by a three-step semi-quantitative immunofluorescence assay using standard monoclonal antibodies specific for each of the four human IgG subclasses. In the rheumatoid sera, the serum level of IgG1 was found to be significantly increased and the level of IgG2 significantly decreased with regard to the control sera, while the levels of IgG3 and 4 as well as total IgG were in the normal range. IgG1,2,3, and 4 AKA were detected in 27 (87%), 6 (19%), 4 (13%) and 11 (35%) of the 31 rheumatoid sera, respectively, and were found to be independent of the clinical and biological indices of the disease. In spite of inter-individual heterogeneity, two predominant profiles were distinguished: IgG1 (alone) and IgG(1 + 4), which together represented 18 sera (58%). The large predominance of IgG1 AKA and the quasi-absence of IgG2 AKA suggest that the recognized antigen may be partly comprised of protein. Moreover, the high frequency of occurrence of IgG4 AKA might result from chronic exposure to the eliciting antigen, which could be a genuine autoantigen since we demonstrated that it is also present in the stratum corneum of human epidermis.

Topics: Animals; Arthritis, Rheumatoid; Autoantibodies; Epithelium; Esophagus; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Immunoglobulin Isotypes; Keratins; Rats

Autoantibodies reacting with human pancreatic exocrine cells were investigated by immunofluorescent techniques in 107 patients with Type 1 (insulin-dependent) diabetes mellitus, 20 first-degree relatives of the Type 1 diabetic patients, 347 patients with Type 2 (non-insulin-dependent) diabetes, 34 with alcoholic pancreatitis, 26 with rheumatoid arthritis and 107 normal control subjects. Both immunoblotting analysis and double-immunostaining methods were used to characterize the antigens targeted by the pancreatic exocrine cell autoantibodies. Sera positive for human pancreatic exocrine cell cytoplasm, producing a "fine fibrillar" pattern, were found in 21% (23/107) of the Type 1 diabetic patients. The autoantibodies were present in 39% (15/38) of Type 1 diabetic patients diagnosed within 3 months, and the prevalence decreased with duration of diabetes. The antibodies were of the IgM class in 87% (13/15) of recent-onset Type 1 diabetes cases, but IgG-autoantibodies became more prevalent with increasing duration of diabetes. Three out of 347 (0.9%) Type 2 diabetic patients and 4 of 20 (20%) first-degree relatives of Type 1 diabetic patients had autoantibodies targeted against pancreatic exocrine cells. None of the patients with alcoholic pancreatitis or rheumatoid arthritis and none of the control subjects had these antibodies. Immunoblotting analysis and double-immunostaining demonstrated that the autoantibodies reacted with 40 kilodalton cytokeratin in pancreatic exocrine cell cytoplasm. The antibody was absorbed by the Triton X-100-insoluble fraction of pancreatic extract. These results indicate the presence of distinct autoantibodies to pancreatic exocrine cells in Type 1 diabetes. This suggests the provocative concept that the cytoskeletal system of pancreatic exocrine cells is involved in the pathogenetic process of Type 1 diabetes.

Topics: Adolescent; Adult; Alcoholism; Arthritis, Rheumatoid; Autoantibodies; Chronic Disease; Diabetes Mellitus, Type 1; Family; Female; Fluorescent Antibody Technique; Humans; Islets of Langerhans; Keratins; Male; Pancreas; Pancreatitis; Reference Values

Serum and synovial fluid of 20 patients with classical or definite rheumatoid arthritis (RA) were tested for antikeratin antibodies (AKA) by indirect immunofluorescence using rat esophagus as antigen. AKA were found in 80% of the RA patients, in serum as well as in synovial fluid. None of the 54 serum control patients were AKA positive in serum. None of the 17 synovial fluid control patients were AKA positive in synovial fluid. F(ab)'2 fragments prepared from AKA positive RA serum retained antibody activity. AKA belonged to the IgG class of immunoglobulins. Corrected for the lower IgG content in synovial fluid, AKA constituted a higher percentage of the IgG in synovial fluid than in serum. This could imply a possibility of local production of AKA in the joint.

Topics: Adult; Aged; Antibodies; Arthritis, Rheumatoid; Female; Humans; Immunoglobulin G; Keratins; Male; Middle Aged; Synovial Fluid

Serum antibodies to the stratum corneum of rat oesophagus epithelium, so-called 'antikeratin antibodies', have been largely demonstrated in rheumatoid arthritis (RA). IgM and IgG antibodies to this epithelium were studied by semiquantitative immunofluorescence in 528 patients with perfectly characterised rheumatic diseases, including 178 with classical or definite RA. Histological analysis of IgG antibodies showed that only antibodies which produce a linear laminated pattern restricted to the stratum corneum (IgG antikeratin antibodies) are highly specific for RA; all the other labelling patterns are not disease specific. By a semiquantitative evaluation of the stratum corneum fluorescence intensity it was shown that the diagnostic value of IgG antikeratin antibodies closely depends on their titre and it was established in objective conditions that the sensitivity is 43.26% when the specificity reaches 99.14%. A high titre of IgG antikeratin antibodies was actually pathognomonic for RA. Both the histological and semi-quantitative analyses showed that IgM antibodies to rat oesophagus epithelium, though frequently detected, are of no diagnostic value, either for RA or for any other rheumatic disease that was studied. From a review of all the international reports on IgG antikeratin antibodies it was found that, to date, 4080 patients, including 1694 with RA, have been assayed for antikeratin antibodies by 11 different research groups. Analysis of all the results obtained under comparable technical conditions showed that IgG antikeratin antibodies constitute the most specific serological criterion for the diagnosis of RA. Furthermore, it was found that their incidence does not depend on disease duration: they are present in one third of rheumatoid factor negative patients with RA, and they seem to be related to disease severity or activity, or both. Their detection in the diagnosis of rheumatic diseases should become systematic.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Animals; Arthritis, Rheumatoid; Autoantibodies; Biomarkers; Epithelium; Esophagus; Humans; Immunoglobulin G; Immunoglobulin M; Keratins; Middle Aged; Rats

Antibodies to rheumatoid arthritis nuclear antigen (RANA) are four- to sixfold increased in sera from patients with rheumatoid arthritis (RA), whereas levels of antibodies to other EBV encoded antigens are slightly elevated or normal. We have demonstrated that the major epitopes recognised by anti-RANA antibodies are represented by a synthetic peptide, P62, corresponding to part of the internal repeat sequence which contains only the amino acids glycine and alanine. In an enzyme-linked immunosorbent assay, anti-P62 antibodies in rheumatoid arthritis sera were four fold higher than healthy and disease controls. By contrast, levels of antibodies to a cloned fusion protein, representing the C-terminus of EBNA-1 and excluding the IR3 region, were normal in RA, but elevated fivefold in nasopharyngeal carcinoma (NPC). Affinity purified anti-P62 antibodies reacted with EBNA-1 and RANA but also with a 60 kD protein present in tissue extracts which has been tentatively identified as cytokeratin. This suggests that the specific increase of anti-P62 antibodies in RA may be due to cross-reactions with autoantibodies to structural proteins with repeat sequences containing glycine. Such sequences are found in cytokeratin and proteoglycans, suggesting that anti-P62 (and hence anti-RANA) antibodies may be cross-reactive antibodies of pathogenic significance in RA, though not necessarily indicating an aetiological role for EBV.

Topics: Alanine; Amino Acid Sequence; Antibodies, Antinuclear; Antigens, Viral; Arthritis, Rheumatoid; Autoantigens; Cross Reactions; Epitopes; Epstein-Barr Virus Nuclear Antigens; Glycine; Herpesvirus 4, Human; Humans; Keratins; Peptide Fragments; Peptides

A method to determine antikeratin antibodies (AKA) is described. AKA were detected by indirect immunofluorescence technique on rat esophagus as antigen in sera of patients with definite rheumatoid arthritis (RA). The frequency of AKA in rheumatoid factor (SCAT/Waaler-Rose) positive RA was 64% and in SCAT-negative RA, 28%. Of 61 control patients with non-RA rheumatic diseases, none was AKA-positive. Of healthy controls, 2.5% were AKA-positive. In serum from 88 definite RA patients, AKA were compared with precoded clinical features. A highly significant correlation to AKA was found with the presence of rheumatoid hand deformity. Some correlation to positive SCAT titre and s-Haptoglobin was observed. Our study suggests that determination of AKA will be of value in the diagnosis of RA, especially in rheumatoid factor negative cases and that the presence of AKA indicates a more aggressive form--or results of an aggressive course--of the disease.

Topics: Animals; Antibodies; Antibody Specificity; Arthritis, Rheumatoid; Female; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Keratins; Male; Middle Aged; Rats; Rheumatoid Factor

Cultured keratinocytes were used as allografts to treat 51 patients with chronic venous ulceration or rheumatoid ulcers unresponsive to all previous conventional treatments including split skin grafts. Although early epithelialization could be seen in the centre of some ulcers, a major effect appeared to be healing from the previously indolent edge. This treatment appears to provide some clinical benefit in healing of chronic ulceration.

Topics: Aged; Aged, 80 and over; Arthritis, Rheumatoid; Bandages; Biological Dressings; Cells, Cultured; Chronic Disease; Epidermal Cells; Female; Humans; Keratins; Leg Ulcer; Male; Middle Aged; Skin Transplantation; Transplantation, Homologous; Venous Insufficiency

Topics: Arthritis, Rheumatoid; Autoantibodies; Humans; Keratins; Time Factors

Anti-keratin antibodies have been detected by indirect immunofluorescence on rats esophageal sections in 122 rheumatoid polyarthritis, 100 seropositive and 22 seronegative. The frequency of anti-keratin antibodies is 58 p. cent in seropositive rheumatoid polyarthritis and 41 p. cent in seronegative rheumatoid polyarthritis. Anti-keratin antibodies have a very good specificity (96 p. cent) for rheumatoid polyarthritis since in a group of 105 controls, only 4 sera were found to have a low titre of anti-keratin antibodies (1 ankylosing spondyloarthritis, 2 sclerodermis, 1 healthy subject). The mean titre of antikeratin antibodies is higher in seropositive rheumatoid polyarthritis than in seronegative rheumatoid polyarthritis. Within seropositive rheumatoid polyarthritis, the titre of anti-keratin antibodies is correlated with the titre of rheumatoid factors determined by the latex test (r' = 0.464, p less than 0.01). The presence of anti-keratin antibodies is correlated with the degree of functional handicap evaluated by the functional index of Steinbrocker (p less than 0.02) and with the biological evolution evaluated by the sedimentation rate (p less than 0.001). No correlation was found with accidents of intolerance to fundamental treatments (gold salts, D-penicillamine), especially skin diseases. Anti-keratin antibodies represent therefore a diagnostic marker for seropositive rheumatoid polyarthritis as well as seronegative ones and an evolutive marker of seropositive rheumatoid polyarthritis.

Topics: Adult; Aged; Antibodies; Arthritis, Rheumatoid; Female; Humans; Keratins; Male; Middle Aged

Eight immunological parameters were explored in 257 patients with various rheumatic diseases including 107 rheumatoid arthritis (RA). IgG and IgM antibodies (AB) reactive with the Stratum Corneum (SC) of rat oesophagus or with the SC of human skin were assayed by 1/2 quantitative indirect immunofluorescence, IgG and IgM auto AB to epidermal keratins by a specific ELISA, and total serum G and M immunoglobulins by radial immunodiffusion. At the threshold we chose (99 p. cent specificity), IgG anti SC of rat oesophagus, were found in 50 of 107 (46.7 p. cent) RA patients: 52.5 p. cent in sero + and 39.6 p. cent in sero - ones. The other parameters, separately considered, had no diagnosis value. In Paget disease serum IgM and IgG and all the AB of M isotype were found to be broken down. In all the groups, the isotype AB were found strongly correlated to each other and to serum IgM. The RA sera with specific AB to the rat oesophagus SC, also labeled human skin SC but these labeling were unrelated to the anti-keratins auto AB level. On the contrary, the anti SC AB of G isotype, detectable on human skin in psoriatic rheumatism did not label rat oesophagus. These results confirm the diagnosis value of IgG AB to SC of rat oesophagus, usually called anti-keratins, who appear as a marker for RA. This work shows the relevance of associating specific immunochemical techniques to immunofluorescence, in order to unravel the antigenic complexity of tissular substrata.

Topics: Animals; Antibodies; Arthritis, Rheumatoid; Autoantibodies; Esophagus; Female; Humans; Immunoglobulin G; Immunoglobulin M; Keratins; Male; Rats; Skin

Sera from patients with rheumatoid arthritis (RA), patients with infectious mononucleosis (IM), and blood donors were tested by indirect immunofluorescence for the presence of antikeratin antibody (AKA), antibody to cytoskeletal intermediate filaments of prekeratin or vimentin type (AIFA) and antiperinuclear factor (APF). In 81.9% of the RA sera and 92.5% of the IM sera AIFA of IgM class was found at titres up to and in some cases exceeding 1/160. In blood donors the incidence of AIFA was 26%, at titres not exceeding 1/20. AKA and APF, always of IgG class, were found in 54.2% and 73.6% of rheumatoid sera. A weak correlation was found in RA between the incidence of AIFA and APF. AKA was not present in either IM or blood donor sera, and APF was found in only 2.5% and 3.2% of IM or blood donors respectively.

Topics: Antibodies, Antinuclear; Arthritis, Rheumatoid; Autoantibodies; Humans; Infectious Mononucleosis; Intermediate Filament Proteins; Keratins; Protein Precursors; Vimentin

Tests for antikeratin antibodies (AKA) were performed on 2152 disease-associated and control sera by indirect immunofluorescence (IF) on rat oesophagus substrate. The incidence of AKA was significantly raised in rheumatoid arthritis (37%) in comparison with systemic sclerosis (8%), psoriasis (7%), ankylosing spondylitis (6%), systemic lupus erythematosus (3%), and normal controls (2%). AKA were detected in synovial fluid obtained from patients with rheumatoid arthritis (RA) (48%) but not from patients with other conditions. Further experiments on AKA-positive sera showed reactivity with stratum corneum of rabbit prepuce and lips. A specific rabbit antihuman keratin antiserum was shown, by IF and inhibition studies, to have a different specificity from that of spontaneous human AKA. AKA were associated with the presence of subcutaneous nodules in RA (p = 0.05), but not with Raynaud's phenomenon, Sjögren's syndrome, or HLA-DR4 positivity. Rheumatoid factor (RF) was not associated with AKA either in RA or in RF-positive disease controls.

Topics: Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Connective Tissue Diseases; Fluorescent Antibody Technique; Humans; Keratins; Raynaud Disease; Rheumatoid Nodule; Saliva; Sjogren's Syndrome; Synovial Fluid

Antikeratin antibodies (AKA) were found in the sera of 59% (121/204) of patients with rheumatoid arthritis (RA). There was a significantly higher incidence of AKA (73%) in male patients compared with females (53%) and a correlation between AKA positivity and IgM rheumatoid factor was found. Antibody reactivity was positively associated with the presence of nodules, antinuclear antibody, C-reactive protein and disease severity. AKA would appear to have possible prognostic significance in patients with RA.

Topics: Antibodies; Antibodies, Antinuclear; Arthritis, Rheumatoid; Female; Humans; Immunoglobulin M; Keratins; Male; Middle Aged; Rheumatoid Factor

89 cases of sero-negative rheumatoid arthritis (RA) were compared to 127 cases of sero-positive RA. Anti-perinuclear and anti-keratin antibodies were detected less frequently in the first group (51 vs 67% and 28 vs 33%, respectively), while the inverse was found for anti-nuclear antibodies (28 vs 24%). "Light" rheumatoid factors (RF)--IgG, IgM, IgE, IgA and IgD--were detected in 23.6, 21.3, 17.5, 11.3 and 0 per cent of cases of sero-negative R.A. The evolutive state of these cases was less severe. RF agglutinins were detected in 5 out of 12 samples of synovial fluid tested in cases of sero-negative RA.

Topics: Adult; Aged; Antibodies, Antinuclear; Antigen-Antibody Complex; Arthritis, Rheumatoid; Autoantibodies; Female; Humans; Immunoglobulins; Keratins; Male; Middle Aged; Prognosis; Rheumatoid Factor; Synovial Fluid

The value of testing for antikeratin antibodies (AKA) in the diagnosis of rheumatic diseases was investigated. AKA were found in the serum of 71 (54%) of 131 patients with rheumatoid arthritis (RA) (including 10 rheumatoid factor (RF) negative individuals) but only in 7 (2%) of 266 patients with non-RA rheumatic diseases, in 2 (3%) of 69 patients with miscellaneous immunological diseases and in one of 100 healthy controls. AKA positivity in RA patients correlated with their age and the presence of RF, antinuclear antibodies, subcutaneous nodules, as well as the extent and severity of systemic disease manifestations. Our study suggests that determination of AKA would be of value in the assessment of patients suspected of having RA.

Topics: Antibodies, Antinuclear; Antibody Specificity; Arthritis, Rheumatoid; Autoantibodies; Epithelium; Esophagus; Female; Fluorescent Antibody Technique; Humans; Immunoglobulin G; Immunoglobulin M; Keratins; Male; Middle Aged; Rheumatoid Factor

Anti-keratin antibodies (AKA) were detected in 68 out of 98 patients (69%) with classical or definite rheumatoid arthritis (RA). The intensity of the AKA reaction correlated significantly with articular index (AI), grip strength (GS), erythrocyte sedimentation rate (ESR), serum C-reactive protein (CRP) concentration, serum amyloid A (SAA) protein concentration, the level of antibodies against single stranded DNA (ssDNA) and the IgM rheumatoid factor (RF) titre. A significantly higher number of patients with nodules and Sjögren's syndrome were AKA positive compared with patients without extra-articular features (EAFs) and the AKA titre was significantly greater in the former group. The mechanisms underlying appearance of AKA are not known but may relate to an as yet unidentified structural alteration of keratin in this disease or may just reflect the rheumatoid autoimmune diathesis.

Topics: Adult; Aged; Arthritis, Rheumatoid; Autoantibodies; Blood Sedimentation; C-Reactive Protein; DNA, Single-Stranded; Female; Humans; Keratins; Male; Middle Aged; Rheumatoid Factor; Serum Amyloid A Protein

Serum antibodies reactive with the keratin layer of rat esophagus (AKA) were found in 46 of 80 (57.5%) rheumatoid arthritis (RA) patients. In contrast, AKA were present in only 7 of 82 (9.5%) patients with other types of rheumatic disorders and in 2 of 47 (4.2%) healthy subjects. AKA were not specific for RA, however, because in the former group, AKA were present in 4 of 20 (20%) systemic sclerosis patients and in 3 of 12 (25%) ankylosing spondylitis patients. AKA belong predominantly to the IgG class and are complement fixing. Although found in some RA joint fluids, AKA were not selectively concentrated in the joint fluid. Absorption of RA serum with type I human collagen or with human epidermal keratin did not remove AKA activity. The frequency of AKA in RA patients both negative and positive for DR4 was equal. There was no relationship between the frequency of AKA and the occurrence of other serum autoantibodies such as antibodies to intermediate filaments, smooth muscle, and nuclear antigens. Serum antibody reactive with human stratum corneum found in patients with psoriatic arthritis was shown to be different from AKA. Rabbit antiserum to human keratin did not inhibit the reaction of AKA against the keratin layer of rat esophagus. Autoimmunity to structural proteins including collagen, vimentin intermediate filaments, smooth muscle antigens, and keratin is a characteristic feature of RA.

Topics: Animals; Arthritis, Rheumatoid; Autoantibodies; Cross Reactions; Epidermis; Fluorescent Antibody Technique; Histocompatibility Antigens Class II; HLA-DR4 Antigen; Humans; Keratins; Rats; Synovial Fluid

Antikeratin antibodies (AKA) were found in 38 out of 96 patients with rheumatoid arthritis (RA); they appeared to be quite characteristic to this disease. There was a very low incidence of AKA positivity in the control groups, i.e., 1 out of 62 healthy subjects and 4 out of 158 other patients. With regard to the sensitivity of the test as a diagnostic tool, AKA was found to be weaker than the rheumatoid factor (RF) and the antiperinuclear factor (APF), whereas the specificity was much better than APF and RF. A clear correlation was shown between the titres of AKA and APF (p less than 0.001) and also between AKA levels and inflammation (p less than 0.02).

Topics: Adult; Aged; Antibodies; Arthritis, Rheumatoid; Female; Humans; Keratins; Male; Middle Aged; Rheumatoid Factor

Tests for antiperinuclear factor (APF) demonstrable by indirect immunofluorescence (IF) on smears of human buccal mucosal cells and for antibodies to keratin (AKA) detected on cryostat sections of rat oesophagus were performed on serum from 102 cases of rheumatoid arthritis (RA) and 117 controls. APF was detected in 92% of the cases of RA; positive tests obtained with non-RA sera were generally weaker than those given by the RA group, and the antibody in both RA and non-RA serum was predominantly IgG class. The difficulty in obtaining suitable substrate material previously reported was confirmed, and only 2 satisfactory donors were identified among 27 individuals tested. The incidence of keratin antibodies detected was found to be related to the site from which the tissue was taken; low oesophagus provided the best discrimination between RA and controls (51% and 5% positive respectively), and cardia of the stomach gave the highest incidence of staining in all groups. A laminar staining pattern was seen with most positive sera, but occasionally the keratinised layer was diffusely stained. The presence of AKA showed a marked correlation with both IgM rheumatoid factor and increased Clq binding in RA, but APF did not.

Topics: Antibodies; Antibodies, Antinuclear; Antigen-Antibody Complex; Arthritis, Rheumatoid; Female; Humans; Keratins; Male; Rheumatoid Factor

Antikeratin antibodies reacting in a laminar distribution with keratinised rat oesophagus were found in the sera of a proportion of patients with rheumatoid arthritis but not in healthy controls. In rheumatoid arthritis (RA) the proportion of sera exhibiting this reactivity varied with the site tested in the rat's upper alimentary tract. There were 36.4% of 99 patients with RA who gave positive reactivity to the middle third of the rat oesophagus. This antikeratin reactivity was related to the occurrence of other antitissue antibodies (to reticulin, gastric parietal cells, smooth muscle, mitochondria, or nuclear components) in the same patients with rheumatoid arthritis. It was not related to the duration of early morning stiffness, the Ritchie index, the erythrocyte sedimentation rate, certain acute phase proteins (haptoglobin and C-reactive protein) nor to the levels of haemoglobin or immunoglobulins. Antikeratin antibodies were not specific for rheumatoid arthritis and also occurred in 50% of 16 patients with progressive systemic sclerosis.

Topics: Adult; Aged; Animals; Antibodies; Antibody Specificity; Arthritis, Rheumatoid; Esophagus; Female; Fluorescent Antibody Technique; Humans; Keratins; Male; Middle Aged; Rats

A naturally occurring antibody that reacts with the keratinised tissue of animal oesophagus was found in the serum of 75 out of 129 patients (58%) with classical or definite rheumatoid arthritis (RA) but not in sera from 105 healthy people. Detection of the antibody, which is unrelated to rheumatoid factor, is more specific for RA than the reaction in the sheep-cell agglutination test but less sensitive.

Topics: Adolescent; Adult; Aged; Animals; Antibodies; Arthritis, Rheumatoid; Female; Fluorescent Antibody Technique; Haplorhini; Humans; Keratins; Male; Mice; Middle Aged; Rats; Rheumatoid Factor

Topics: Alpha-Globulins; Arthritis, Rheumatoid; Beta-Globulins; Blood Protein Electrophoresis; Brachial Plexus Neuritis; Cerebrovascular Disorders; Electrophoresis, Disc; gamma-Globulins; Gold; Gout; Humans; Injections, Intramuscular; Injections, Intravenous; Keratins; Plasmacytoma; Protein Binding; Serum Albumin; Thiosulfates

Topics: Animals; Antibodies; Antibodies, Anti-Idiotypic; Antibodies, Antinuclear; Arthritis, Rheumatoid; Fluorescent Antibody Technique; Goats; Humans; Keratins; Mouth Mucosa