lactoferrin and Sjogren-s-Syndrome

To evaluate the potential of lactoferrin (Lf) as a diagnostic biomarker for ocular diseases using a meta-analytic approach.. All original studies reporting an estimate of the average Lf concentration in healthy subjects and those affected by ocular diseases were searched up to March 2020. The DerSimonian and Laird method was used to calculate the random effects pooled mean difference and the corresponding 95% confidence interval (CI) in Lf concentration between healthy subjects and those affected by dry eye (DE), Sjögren syndrome (SS), and diabetic retinopathy, separately. The presence of between-study heterogeneity was evaluated using the Cochran's Q test and the I2 index. Stratified analyses were performed to assess potential sources of heterogeneity and influence and cumulative analyses to evaluate the robustness of the results obtained. Publication bias was also evaluated using funnel plot and the Egger's test.. The pooled mean differences in Lf concentrations between healthy subjects and those with DE, Sjögren syndrome, and diabetic retinopathy were respectively 0.62 (95% CI, 0.35-0.89) for DE, 3.78 (95% CI, -6.64 to 14.17), and 0.19 (95% CI, -4.00 to 4.39). Regarding DE, the stratified analysis showed that geographical area (P value Q test < 0.0001) and sample size (P < 0.0005) were sources of heterogeneity. Moreover, no study substantially influenced the results obtained and the pooled mean difference became statistically significant after a sample size of 220. Publication bias may affect the results of DE.. The results of the current meta-analysis suggest that Lf level in tears is a good candidate as dry eye syndrome diagnostic biomarker.

Topics: Biomarkers; Diabetic Retinopathy; Dry Eye Syndromes; Eye Proteins; Humans; Lactoferrin; Sjogren's Syndrome; Tears

To assess the available data and the place of salivary analysis in the diagnosis of Sjögren's syndrome (SS).. A Medline search of English language articles published between 1985 and 1996 and a manual search of the reference lists of relevant articles formed the data sources. These were combined with our clinical and experimental experience in this field. Each method of salivary analysis was assessed according to study design, type of saliva used for the study, sensitivity/ specificity for the diagnosis of SS, and correlation to the histopathological findings.. Increased levels of salivary Na+, immunoglobulins (particularly IgA), anti-Ro and La antibodies, lactoferrin, lysozyme, beta 2 microglobulin, prostaglandin E2, thromboxane B2, interleukin-6, and hyaluronic acid have been detected in various studies. Results varied according to the different methods used for saliva collection.. Although many changes have been detected in various constituents of saliva in SS patients, no test has proved sensitive or specific enough for diagnosing SS.

Topics: Autoantibodies; beta 2-Microglobulin; Biomarkers; Electrolytes; Humans; Immunoglobulin A, Secretory; Lactoferrin; Saliva; Salivary Glands; Sensitivity and Specificity; Sjogren's Syndrome

Diagnosis of a dry eye is facilitated by prompt recognition of pertinent signs and symptoms and by utilisation of those office and laboratory procedures which help to confirm the diagnosis. Prior knowledge of those systemic diseases associated with keratoconjunctivitis sicca (KCS) alert the practitioner to a possible dry eye state. Conversely, a diagnosis of KCS may prompt recognition of a hitherto unsuspected systemic disease. In this review, I will discuss the signs and symptoms of KCS, its association with various systemic conditions, as well as the tests and procedures that contribute to its diagnosis.

Topics: Adolescent; Adult; Blepharitis; Child; Cornea; Dysautonomia, Familial; Epithelium; Erythema Multiforme; Humans; Keratoconjunctivitis; Lactoferrin; Muramidase; Osmolar Concentration; Pemphigoid, Benign Mucous Membrane; Rose Bengal; Sarcoidosis; Sjogren's Syndrome; Tears

Topics: Administration, Oral; Cornea; Cross-Over Studies; Female; Humans; Lactoferrin; Male; Middle Aged; Prospective Studies; Sjogren's Syndrome; Tablets, Enteric-Coated; Tears

Sjögren syndrome (SS) or dry eye disease (DED) is one of the most complicated ocular surface diseases. The goal of this study is to elucidate the relationship of the changes in clinical indices of tear film (TF) homeostasis with respect to tear components to allow for SS-DED monitoring and avoid stably controlled SS-DED patients from re-entering a vicious cycle. This prospective case-control study compared stable SS-DED patients with non-SS-DED control from several aspects, including clinical indices for TF homeostasis, 2 DED diagnostic biomarkers (MMP-9 and lactoferrin), and the proteome of flush tears. Compared with non-SS-DED controls, stably controlled SS-DED subjects had less tear secretion and higher ocular surface inflammation, a higher concentration ratio of tear MMP-9/lactoferrin, a more diverse tear proteome, and lower spectral intensities of lipocalin-1, lacritin, and prolactin-inducible protein among the abundant tear proteins. For stable SS-DED patients, the concentration ratio of tear MMP-9/lactoferrin and the corrected lipocalin-1 signal was positively correlated with ocular inflammation and TF stability, respectively. MMP-9 released from stressed ocular surface epithelium and lipocalin-1 secreted from the energetic lacrimal gland are two tear biomarkers responding well to TF homeostasis. The tear proteomics approach through flush tears is a promising method for monitoring SS-DED patients with a standardized sampling procedure and lactoferrin-corrected analysis.

Topics: Biomarkers; Case-Control Studies; Dry Eye Syndromes; Eye Proteins; Female; Humans; Lactoferrin; Male; Middle Aged; Proteomics; Sjogren's Syndrome; Tears

Topical therapy is effective for dry eye, and its prolonged effects should help in maintaining the quality of life of patients with dry eye. We previously reported that the oral administration of rebamipide (Reb), a mucosal protective agent, had a potent therapeutic effect on autoimmune lesions in a murine model of Sjögren's syndrome (SS). However, the effects of topical treatment with Reb eyedrops on the ocular lesions in the murine model of SS are unknown.. Reb eyedrops were administered to the murine model of SS aged 4-8 weeks four times daily. Inflammatory lesions of the extraorbital and intraorbital lacrimal glands and Harderian gland tissues were histologically evaluated. The direct effects of Reb on the lacrimal glands were analyzed using cultured lacrimal gland cells. Tear secretions of Reb-treated mice were significantly increased compared with those of untreated mice. In addition to the therapeutic effect of Reb treatment on keratoconjunctivitis, severe inflammatory lesions of intraorbital lacrimal gland tissues in this model of SS were resolved. The mRNA expression levels of IL-10 and mucin 5Ac in conjunctival tissues from Reb-treated mice was significantly increased compared with those of control mice. Moreover, lactoferrin production from lacrimal gland cells was restored by Reb treatment.. Topical Reb administration had an anti-inflammatory effect on the ocular autoimmune lesions in the murine model of SS and a protective effect on the ocular surfaces.

Topics: Administration, Ophthalmic; Alanine; Animals; Anti-Inflammatory Agents; Cells, Cultured; Disease Models, Animal; Drug Administration Schedule; Female; Gene Expression Regulation; Humans; Interleukin-10; Keratoconjunctivitis; Lacrimal Apparatus; Lactoferrin; Mice; Mucin 5AC; Quinolones; Sjogren's Syndrome

However, there are some informations on the salivary glands involvement in systemic sclerosis, and there is a lack of any data about salivary glands function depending on systemic sclerosis subsets.. The unstimulated and stimulated salivary flow, the activity of peroxidase, the total amount of lactoferrin, lysozyme and sIgA were determined in two subgroups of systemic sclerosis and healthy controls.. In the unstimulated saliva of both patients groups, the salivary flow, the output of total protein and peroxidase activity were significantly lower; the total: sIgA and lactoferrin were significantly higher as compared with the control. In the stimulated saliva of the patients with limited form, the total lysozyme and peroxidase activity were significantly higher than in the control. In the stimulated saliva of the patients with diffused form, the salivary flow was significantly lower and the total sIgA and peroxidase activity were significantly higher than in the control.. Systemic sclerosis regardless of its subset affects salivary defense system of human unstimulated and stimulated saliva. Patients with the limited form experience the same impairment of the submandibular glands function as compared with patients with the diffused form. Only patients with the diffused form are deficient in respect of stimulated saliva secretion; the parotid glands of the patients with the limited form have a good secretory capacity in comparison with the healthy control.

Topics: Adaptive Immunity; Adult; Aged; Antibodies, Antinuclear; Case-Control Studies; DMF Index; Female; Humans; Immunity, Innate; Immunoglobulin A, Secretory; Lactoferrin; Middle Aged; Muramidase; Parotid Gland; Periodontal Index; Peroxidase; Saliva; Salivary Proteins and Peptides; Scleroderma, Diffuse; Scleroderma, Limited; Secretory Rate; Sjogren's Syndrome; Submandibular Gland

The ability to probe the protein content of human tear fluid has enormous potential for deepening our understanding of ocular and systemic disease pathology and enabling novel noninvasive tear-based diagnostic technologies. To overcome current challenges in tear proteomic measurements, we report on the first microfluidic homogeneous immunoassay capable of making rapid, quantitative, and specific measurements of endogenous tear protein biomarkers in human tear fluid. Lactoferrin (Lf) is a tear-specific biomarker for Sjögren's syndrome (SS), a serious systemic autoimmune disease currently diagnosed through rudimentary volumetric and surface chemistry measurements and an invasive lip biopsy. We detail optimization of a homogeneous electrophoretic immunoassay for Lf in <1 μL of tear fluid at clinically relevant concentrations. In particular, we present assay development details and a final assay that enables quantification of Lf in <5 s in a clinically relevant range for SS diagnostics. Characterization suggests the on-chip assay is accurate to within 15% of ELISA, specific (<15% nonspecific signal), and with a lower limit of detection of 3 ± 2 nM Lf in human tear matrix. Additionally, we develop and characterize a protocol for eluting proteins from nitrocellulose Schirmer strips, the clinical de facto standard for tear collection and storage. We relate on-chip measured Lf concentrations back to ocular surface concentrations for the first time to our knowledge. Taken in sum, this work details important steps toward (1) expanding the set of proteins quantified by electrophoretic immunoassays to encompass a wider range of isoelectric points than has been reported, (2) creating a first-in-kind translatable assay with clinical relevance to SS diagnostics, and (3) expanding the analytical toolkit available for rapid tear protein measurements, as is relevant to the advancement of basic research and clinical medicine.

Topics: Biomarkers; Case-Control Studies; Cohort Studies; Eye Proteins; Humans; Immunoassay; Lactoferrin; Microfluidics; Pilot Projects; Proteomics; Sjogren's Syndrome; Tears

To identify the most significant salivary biomarkers in Sjögren's syndrome (SS) using proteomic methods.. Parotid saliva from 20 non-SS subjects and 41 primary SS patients was analysed. Protein expression profiles for each sample were generated by surface-enhanced laser desorption/ionization time-of-flight-mass spectrometry (SELDI-TOF-MS). Mean peak intensities of SS patients and non-SS subjects were compared by univariate analyses. Samples pooled by diagnosis (SS and non-SS) and labelled with different Cy dyes were compared by two-dimensional difference gel electrophoresis (2D-DIGE). Two protein levels that were most significantly different by SELDI-TOF-MS and 2D-DIGE were validated by enzyme-linked immunosorbent assay in individual samples.. SELDI-TOF-MS of 10-200 kDa peaks revealed eight peaks with >2-fold changes in the SS group that differed from non-SS at P < 0.005. Peaks of 11.8, 12.0, 14.3, 80.6 and 83.7 kDa were increased, while 17.3, 25.4, and 35.4 kDa peaks were decreased in SS samples. 2D-DIGE identified significant increases of beta-2-microglobulin, lactoferrin, immunoglobulin (Ig) kappa light chain, polymeric Ig receptor, lysozyme C and cystatin C in all stages of SS. Two presumed proline-rich proteins, amylase and carbonic anhydrase VI, were reduced in the patient group. Three of these ten biomarkers have not been associated previously with SS.. The salivary proteomic profile of SS is a mixture of increased inflammatory proteins and decreased acinar proteins when compared with non-SS. Future studies will test the ability of these biomarker levels, alone and in combination, to diagnose the salivary component of SS.

Topics: Amylases; beta 2-Microglobulin; Biomarkers; Carbonic Anhydrases; Case-Control Studies; Cystatin C; Cystatins; Electrophoresis, Gel, Two-Dimensional; Humans; Lactoferrin; Muramidase; Parotid Gland; Protein Subunits; Proteomics; Receptors, Polymeric Immunoglobulin; Saliva; Sjogren's Syndrome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Statistics, Nonparametric

We analysed and compared electrophoretic tear proteins patterns of healthy subjects and patients with different autoimmune diseases associated with secondary Sjogren's syndrome.. Tears were collected using the Schirmer's method. Proteins were separated by sodium-dodecyl sulfate polyacrylamide gel electrophoresis. The lanes were stained by Coomassie blue and/or silver.. Lactoferrin, albumin, lipocalin and lysozyme were found to be the main components being identified using molecular weight markers.. Electrophoretic analysis of tear proteins patterns is a fast, reproducible and simple method which provides information about the possibility of lacrimal gland involvement in auto-immune diseases.

Topics: Anti-Infective Agents; Autoimmune Diseases; Carrier Proteins; Cysteine Proteinase Inhibitors; Electrophoresis, Gel, Two-Dimensional; Eye Proteins; Humans; Lactoferrin; Lipocalin 1; Muramidase; Sjogren's Syndrome; Tears

We analysed and compared electrophoretic tear protein patterns of healthy subjects and patients with different autoimmune diseases associated with secondary Sjogren's syndrome.. Tears were collected using the Schirmer's method. Proteins were separated by sodium-dodecyl sulfate poliacrylamide gel electrophoresis. The lanes were stained by Coomassie blue and/or silver.. Lactoferrin, albumin, lipocalin and lysozyme were found to be the main components being identified using molecular weight markers.. Electrophoretic analysis of tear proteins patterns is a fast, reproducible and simple method which provides information about the possibility of lacrimal gland involvement in autoimmmune diseases.

Topics: Albumins; Anti-Infective Agents; Autoimmune Diseases; Carrier Proteins; Case-Control Studies; Electrophoresis, Polyacrylamide Gel; Eye Proteins; Humans; Lactoferrin; Lipocalin 1; Muramidase; Sensitivity and Specificity; Sjogren's Syndrome; Tears

In this study, the secretion rate and IgA, albumin and lactoferrin concentrations in minor labial and buccal gland saliva were investigated in individuals with hyposalivation due to primary Sjogren's syndrome (pSS; 10 subjects) or head and neck radiation therapy (RT; 10 subjects) and in their matched controls. Whole saliva was similarly examined. The minor gland saliva flow was measured using the Periotron method. IgA, albumin and lactoferrin concentrations were analysed by ELISA techniques. A general finding was that the flow rate and protein concentrations were lower in labial than in buccal gland saliva. In both hyposalivation groups, the labial minor gland saliva secretion rate was lowered compared to their respective controls. The buccal gland saliva flow rate was significantly reduced in the RT group only. IgA and albumin concentrations were not different from the controls in the labial secretions. The concentration of lactoferrin was increased in the RT group. In buccal saliva, the concentrations of all proteins examined but pSS IgA, were increased compared to the controls. Reduced flow rate and increased protein concentrations were seen for whole saliva where the lactoferrin concentration was higher in RT than in pSS subjects. Thus, our findings suggested that minor gland saliva flow rate and protein concentrations are affected in RT and pSS subjects and to highest extent in the former.

Topics: Adult; Aged; Albumins; Case-Control Studies; Cheek; Enzyme-Linked Immunosorbent Assay; Female; Head and Neck Neoplasms; Humans; Immunoglobulin A, Secretory; Lactoferrin; Lip; Male; Middle Aged; Radiation Injuries; Radiotherapy; Salivary Glands, Minor; Salivary Proteins and Peptides; Salivation; Sjogren's Syndrome; Xerostomia

To verify the hypothesis that protein concentrations, such as lactoferrin, epidermal growth factor (EGF), and aquaporin 5 (AQP5), in tears are abnormal in patients with dry eye.. Prospective case-control study.. One hundred three dry eye patients were divided into three groups: dry eye not associated with the Sjögren syndrome (non-SS; n = 71), Sjögren syndrome (SS; n = 23), and Stevens-Johnson syndrome (SJS; n = 9). Sixteen normal control subjects were also checked. The concentrations of lactoerrin, EGF, and AQP5 were measured by enzyme-linked immunosorbent assay.. The concentration of lactoferrin was significantly decreased in tears of non-SS (P =.0001), SS (P =.00005), and SJS (P =.0006) patients compared with control subjects. The concentration of EGF was significantly decreased in non-SS (P =.0005), SS (P =.00002), and SJS (P =.0001) patients compared with control subjects. The concentration of AQP5 was significantly increased in tears of only SS patients (P =.01) compared with control subjects and increased in tears of only SS patients compared with non-SS patients (P =.007).. The decrease in both lactoferrin and EGF was found not only in SS patients but also in non-SS patients, indicating that tear components in dry eyes differ in their quantity and quality. Quantification of AQP5 increased only in SS patients, suggesting that AQP5 protein leaks into the tears when acinar cells of the lacrimal gland are damaged by lymphocytic infiltration.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Aquaporin 5; Aquaporins; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Eye Proteins; Female; Humans; Lactoferrin; Male; Membrane Proteins; Middle Aged; Prospective Studies; Sjogren's Syndrome; Stevens-Johnson Syndrome; Tears

Little is known about the relationship between lachrymal and salivary gland involvement in Sjögren's syndrome (SS). It is also of interest to know which eye test contributes most to the diagnosis of SS. We investigated the performance of different tear tests and how these tests relate to common serologic and salivary tests in SS.. In patients suspected of SS, the tear breakup time and the tear mucus score were evaluated in addition to the routine tests. Eighty consecutive patients were included, categorized into primary SS (pSS), secondary SS (sSS), and negative for SS.. The tear breakup time and mucus score both performed insufficiently in diagnosing SS, in contrast to the Rose Bengal score. In pSS and sSS patients, a clear correlation was noted between tear and saliva quality and secretion rate, and between the Rose Bengal score and parotid sialography. Increased Rose Bengal scores also correlated significantly with hyperglobulinemia and presence of SSB antibodies in serum, with duration of subjective eye dryness, and with decreased tear gland function.. The Rose Bengal score remains the eye test of choice having the highest specificity for SS. Hyperglobulinemia and especially positive SSB serology may warrant close monitoring of the eyes, since these serum findings appear to relate to the severity of ocular surface damage. Theoretically, a positive evaluation of either the ocular or oral component, in addition to positive serology or histopathology, could be sufficient to diagnose the syndrome for clinical purposes.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antinuclear; Disease Progression; Dry Eye Syndromes; Female; Fluorescent Dyes; Humans; Lactoferrin; Male; Middle Aged; Mucus; Rose Bengal; Salivary Gland Diseases; Sensitivity and Specificity; Sjogren's Syndrome; Tears

There are several reasons for hyposalivation, each affecting the salivary composition in different ways. The aim of this study was to analyze and compare lactoferrin, amylase and mucin MUC5B in stimulated whole saliva collected from subjects with hyposalivation of different origins and to relate the results to the presence of some microbial species associated with oral disorders. Albumin was determined as a marker of serum leakage. The characteristic feature for subjects with radiation-induced hyposalivation was a large increase in lactoferrin, probably due to leakage through inflamed mucosal tissues, while it was a high albumin content for the group with primary Sjögren's syndrome, probably due to disruption of the fragile mucosa. The saliva composition in subjects with hyposalivation of unknown origin or due to medicines was close to that in the healthy controls. All three hyposalivation groups tended to display a decrease in the concentrations of MUC5B and amylase. None of the microbial species analyzed (streptococci, mutans streptococci, Lactobacillus spp., Fusobacterium nucleatum, Prevotella intermedia/Prevotella nigrescens, Candida albicans, Staphylococcus aureus and enterics) correlated with concentration of MUC5B in saliva. The RT group, having the highest concentration of lactoferrin, had the lowest median number of F. nucleatum and was the only group in which median number of P. intermedia/P. nigrescens was zero.

Topics: Adult; Aged; Amylases; Analysis of Variance; Candida albicans; Colony Count, Microbial; Enterobacteriaceae; Female; Fusobacterium nucleatum; Humans; Lactobacillus; Lactoferrin; Male; Middle Aged; Mucin-5B; Mucins; Prevotella; Prevotella intermedia; Radiotherapy; Saliva; Salivary Proteins and Peptides; Secretory Rate; Serum Albumin; Sjogren's Syndrome; Staphylococcus aureus; Statistics as Topic; Streptococcus; Streptococcus mutans; Xerostomia

The routine clinical diagnosis of sicca syndrome remains difficult; the results of the standard tests, such as the Schirmer test, tear film break-up time and the rose Bengal test, correlate neither with the course of the disease nor with one another.. We introduce two procedures that can be used to differentiate patients with sicca syndrome from healthy individuals on the basis of tear fluid protein patterns. Electrophoretic separation of the tear proteins or measurement by high-performance liquid chromatography (HPLC) was followed by digital image processing and multivariate discriminant analysis.. In addition to analysis of tear protein patterns, these methods permit diagnostic classification. Statistical evaluation reveals whether an unidentified sample is to be classified as sicca syndrome or "healthy". Both HPLC analysis and protein electrophoresis detect differences in protein patterns between the tear fluid of healthy individuals and patients with sicca syndrome and point to a diagnosis accordingly.. Both of the techniques presented - electrophoresis and HPLC - could potentially be used for diagnostic purposes in the detection of sicca syndrome. The HPLC method of tear protein analysis is more reliable, lends itself more readily to automation and achieved greater success rates in the experiments we describe; for these reasons it is the preferred approach.

Topics: Albumins; Chromatography, High Pressure Liquid; Diagnosis, Differential; Discriminant Analysis; Electrophoresis; Humans; Immunoglobulin A; Lactoferrin; Muramidase; Prealbumin; Proteins; Sjogren's Syndrome; Tears

Sjögren's syndrome is an autoimmune condition affecting the lacrimal and salivary glands and can be associated with rheumatoid arthritis and primary biliary cirrhosis. Parotid salivas collected from patients and normal controls were analysed for lactoferrin, IgA and beta2-microglobulin (measured by ELISA), and cystatin (measured by a enzyme inhibition assay). Output data provided less variable means, whilst expressing results as a proportion of the total protein provided greater specificity as markers for Sjögren's syndrome. Levels of specificity for IgA, lactoferrin and beta2-microglobulin were all high (100, 95 and 100%, respectively). Sensitivity levels of these markers (but not cystatin) tended to be similar for Sjögren's syndrome secondary to primary biliary cirrhosis (IgA, 25%; lactoferrin, 63%; and beta2-microglobulin, 50%), compared to Sjögren's syndrome secondary to connective tissue diseases such as rheumatoid arthritis (IgA, 50%; lactoferrin, 86%; and beta2-microglobulin; 38%).

Topics: Arthritis, Rheumatoid; beta 2-Microglobulin; Case-Control Studies; Connective Tissue Diseases; Cystatins; Humans; Immunoglobulin A, Secretory; Lactoferrin; Liver Cirrhosis, Biliary; Parotid Gland; Saliva; Salivary Proteins and Peptides; Secretory Rate; Sjogren's Syndrome

Human parotid salivas were collected from patients with secondary Sjögren's syndrome and controls without disease or with drug-induced xerostomia. Parotid glycoproteins were separated by gradient sodium dodecyl sulphate gel electrophoresis (SDS-PAGE), electroblotted onto nitrocellulose membrane and probed with biotinylated lectins of characterised sugar specificities. The binding patterns of lectins from Maclura pomifera (MPA) and Arachis hypogaea (PNA) indicated that many parotid glycoproteins have sialylated O-linked glycans and that sialylation is not affected by disease. Binding by lectins from Ricinus communis (RCA-1), Limax flavus (LFA), Lotus tetragonolobus (LTA) and Ulex europaeus (UEA-1) appeared unaltered in secondary Sjögren's syndrome, suggesting no obvious change in N-glycosylation of parotid glycoproteins. Variations in binding patterns of most lectins was attributable to subject-to-subject variations in recognised polymorphic proteins. Dolichos biflorus agglutinin (DBA) consistently showed increased binding to a 75 kDa (Mr) protein in salivas from patients with secondary Sjögren's syndrome. The binding protein was identified as lactoferrin but found not to contain N-acetylgalactosamine, the sugar to which DBA binds. Binding of DBA to lactoferrin was dependent upon its saturation with iron, modified SDS-PAGE under nonreducing conditions resolved iron-free and iron-saturated lactoferrins and demonstrated increased levels of the iron-saturated form in secondary Sjögren's syndrome. Lectin binding studies of purified lactoferrins from saliva, milk, and polymorphonuclear neutrophils suggested that raised levels of lactoferrin in saliva originate from salivary cells and not from inflammatory cells. These results suggest that DBA binding provides greater specificity as an indicator of salivary gland disease than measurement of lactoferrin levels alone.

Topics: Biotinylation; Electrophoresis, Polyacrylamide Gel; Glycoproteins; Glycosylation; Humans; Iron; Lactoferrin; Lectins; N-Acetylneuraminic Acid; Parotid Gland; Peanut Agglutinin; Plant Lectins; Saliva; Sjogren's Syndrome; Xerostomia

The purpose of this study was to examine the effect of salivary flow rate on the levels of antimicrobial salivary proteins in 24 patients with Sjögren's syndrome and 22 age- and race-matched healthy control subjects.. Parameters examined included stimulated salivary flow rate, total salivary protein, lactoferrin, lysozyme, amylase, and secretory immunoglobulin A.. The mean total salivary protein and the mean salivary amylase were significantly greater in patients than in controls. However, no significant difference was observed in the mean stimulated salivary flow rates or the levels of lactoferrin, lysozyme, or secretory immunoglobulin A of patients and controls. To examine the effect of salivary flow rate on the levels of salivary antimicrobial protein, the levels of these proteins in patients with salivary flow rate of < or = 0.3 mL/min per gland were compared to those in healthy controls with salivary flow rate > or = 0.4 mL/min per gland. Analyses showed the levels of lactoferrin to be significantly higher among patients than among controls.. The levels of salivary amylase and lactoferrin may be influenced by the levels of salivary output in patients with Sjögren's syndrome. The relationship between salivary flow rate and the levels of amylase and lactoferrin is not clear at the present time.

Topics: Adult; Aged; Amylases; Case-Control Studies; Female; Humans; Immunoblotting; Immunoglobulin A, Secretory; Lactoferrin; Male; Middle Aged; Muramidase; Saliva; Salivary Proteins and Peptides; Secretory Rate; Sjogren's Syndrome; Statistics, Nonparametric

The incidence, specificity and clinical significance of positivity for serum antineutrophil cytoplasmic antibody (ANCA) was investigated in 60 patients with primary Sjögren's syndrome (SjS). The indirect immunofluorescence (IIF) technique and an enzyme-linked immunosorbent assay (ELISA) were used to measure ANCA. Purified myeloperoxidase (MPO), lactoferrin (LF), cathepsin-G (CTG) and elastase (HLE) served as ANCA antigens for the ELISA. Ten (16.7%) of the 60 SjS patients showed positivity by IIF for perinuclear, but not cytoplasmic, ANCA. Four of the 60 sera were shown to be positive for LF, four for MPO, 0 for CTG and 0 for HLE by ELISA. There was no correlation between ANCA positivity and clinical features. ANCA in patients with SjS might be an epiphenomenon of polyclonal B-cell activation.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Antineutrophil Cytoplasmic; Cathepsin G; Cathepsins; Enzyme-Linked Immunosorbent Assay; Female; Fluorescent Antibody Technique, Indirect; Humans; Lactoferrin; Male; Middle Aged; Pancreatic Elastase; Peroxidase; Serine Endopeptidases; Sjogren's Syndrome

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Diagnostic Errors; Diagnostic Techniques, Ophthalmological; Female; Humans; Keratoconjunctivitis Sicca; Lactoferrin; Male; Middle Aged; Probability; Reproducibility of Results; Sjogren's Syndrome; Tears

To assess the course of tear gland function of patients with keratoconjunctivitis sicca (KCS) associated with primary (KCS-PSS) or secondary Sjögren's syndrome (KCS-SSS), and of patients with KCS not related to Sjögren's syndrome (KCS-NS).. In 106 patients with dry eye an ophthalmic diagnosis of KCS was made. Subsequent evaluations revealed a diagnosis of KCS-PSS in 31, KCS-SS in 19, and KCS-NS in 56 patients. Follow up assessments have been performed 10-12 years after initial diagnosis.. At baseline and at follow up tear gland function tests were worse in patients with KCS-PSS compared with the other forms of KCS. At follow up in the KCS-SSS patient group the tear gland function variables returned to marginal normal limits. In contrast with expectation, a marked improvement of the tear gland function variables in the KCS-NS patient group was noted.. In KCS-PSS patients tear gland function is characterised by a steady state situation. In KCS-SSS patients the normalisation of tear gland function variables most probably reflects a remission of the underlying disease. In view of the overall improvement in KCS-NS patients the term age related KCS should be avoided.

Topics: Disease Progression; Female; Follow-Up Studies; Humans; Keratoconjunctivitis Sicca; Lacrimal Apparatus; Lactoferrin; Male; Middle Aged; Muramidase; Sjogren's Syndrome; Statistics, Nonparametric; Tears

To compare the protein composition of tear fluid obtained from patients with primary Sjögren's syndrome, patients with other connective tissue diseases and control individuals.. SDS polyacrylamide gel electrophoresis followed by staining with Coomassie blue and Western blotting.. Comparison revealed the presence of a characteristic difference in the ratio of intensity between the albumin and lactoferrin bands. An albumin:lactoferrin ratio above 2:1 was significantly more common in patients with primary Sjögren's syndrome than in patients with other connective tissue diseases or the controls.. An albumin:lactoferrin ratio above 2:1 may therefore prove of use when diagnosing 1(0)SS. Used as a test, its sensitivity was 67% and its specificity 100%.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Blotting, Western; Connective Tissue Diseases; Electrophoresis, Polyacrylamide Gel; Eye Proteins; Female; Humans; Lactoferrin; Male; Middle Aged; Sensitivity and Specificity; Sjogren's Syndrome; Tears

Results of dry eye tests and ocular symptoms were compared and correlated in patients with primary Sjögren's syndrome (1 degree SS), in patients with connective tissue disease differing from 1 degree SS, and in normal controls. Patients with 1 degree SS had many and pronounced ocular complaints, however, non-diagnostic for the disease. Break-up time and Schirmer-1 test results below 10 mm/5 min both had high sensitivity but low specificity, whereas the reverse was true for Rose-Bengal score and Schirmer-1 test below 5 mm/5 min. Presence of snake-like chromatin in conjunctival imprints and the lactotest on tear fluid did not qualify as alternative tests since they had very low specificity and were less sensitive than the Schirmer-1 test and break-up time. Cornea sensitivity was not found to be an appropriate test at all. In 21% of eyes the presence of keratoconjunctivitis sicca changed from one consultation to the next in patients with 1 degree SS. Examination for keratoconjunctivitis sicca should therefore be repeated in test negative cases where symptoms indicate 1 degree SS.

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Diagnostic Tests, Routine; Female; Humans; Keratoconjunctivitis Sicca; Lactoferrin; Male; Middle Aged; Prevalence; Sensitivity and Specificity; Sjogren's Syndrome; Surveys and Questionnaires; Tears

We studied the relationship between the severity of ocular surface damage and the level of tear lactoferrin in primary and secondary Sjögren's syndrome and keratoconjunctivitis sicca not associated with Sjögren's syndrome. A significant negative correlation was found between Rose Bengal staining score and level of tear lactoferrin in all three groups. Analysis of covariance disclosed no significant differences in regression lines for Rose Bengal staining score vs tear lactoferrin level among the three groups. The three regression lines appeared to be identical to each other. These findings indicate that the severity of ocular surface damage due to dry eye largely depends on the tear secretory function of the lacrimal gland, and that the function of the lacrimal gland can be evaluated by determination of level of tear lactoferrin using the same standards regardless of differences in pathogenesis of underlying diseases.

Topics: Adolescent; Adult; Aged; Analysis of Variance; Dry Eye Syndromes; Eye Proteins; Female; Humans; Keratoconjunctivitis Sicca; Lactoferrin; Male; Middle Aged; Rose Bengal; Sjogren's Syndrome; Tears

To establish a definitive set of diagnostic criteria in a multicentre European study a selected number of oral and ocular tests were performed on a large number of patients with Sjögrens Syndrome (SS) and controls. The diagnostic accuracy of each test for patients with primary and secondary SS and for controls at different ages, was studied.. Each centre received a clinical chart describing the series of tests to be conducted. The tests included: questionnaires for dry eye and dry mouth symptoms, Schirmer's-I-test (ScT), tear fluid lactoferrin level (TFLL), break-up time (BUT) and rose Bengal score (RBS) for the eye evaluation; unstimulated and stimulated whole saliva collection (UWSC and SWSC), salivary gland scintigraphy (SGS), parotid sialography (PS) and minor salivary gland biopsy (MSGB) for oral involvement.. Data from 22 centres and 11 countries was collected on a total of 447 patients with SS (246 with primary SS and 201 with secondary SS) and 246 controls (of whom 113 had a connective tissue disease without SS). Among the ocular symptoms, the feeling of dry eye and 'sand in the eye' were the ones most commonly recorded in patients with SS. Similarly, the feeling of dry mouth, appearing either spontaneously or when the patient was eating or breathing, was the most frequent subjective oral symptom. Among the ocular tests, ScT showed the best balance between sensitivity and specificity (76.9% and 72.4% respectively), while RBS was the most specific test (81.7%). ScT and RBS gave also sufficiently concordant results. TFLL and BUT gave considerably less reliable results, which were not concordant with each other or with the other ocular tests. The quantitative lacrimal tests ScT and TFLL produced significantly different results in elderly controls, while RBS did not. Abnormal results for all of the ocular tests were less marked and less frequent in patients with secondary SS than in those with primary SS. The oral tests (except SWSC) were generally more reliable than the ocular tests in diagnosing SS. In particular, PS was the most specific diagnostic tools (100%), while MSGB (where the presence of at least one inflammatory focus was considered as indicative for the diagnosis) showed a good balance between sensitivity and specificity (82.4% and 86.2%, respectively). The tests showed a good degree of agreement, and, with the exception of UWSC, were not influenced by age. In the oral, as in the ocular tests, abnormal results were less frequent and less marked in patients with secondary SS.. The results clearly show that ScT and RBS (for the eye evaluation), and SGS, PS, MSGB and UWSC (for salivary gland involvement) are the most reliable tests for the diagnosis of SS. The clinician should be aware, however, that the test results may vary depending on the age of the patient and the type of SS (primary or secondary).

Topics: Adult; Age Factors; Aged; Dry Eye Syndromes; Eye Diseases; Female; Humans; Lactoferrin; Male; Middle Aged; Mouth Diseases; Parotid Gland; Radiography; Radionuclide Imaging; Saliva; Salivary Glands; Sensation Disorders; Sensitivity and Specificity; Sjogren's Syndrome; Tears

We have compared clinical (Schirmer I test, BUT and rose bengal staining), laboratory (lysozyme and lactoferrin tear levels) and histological tests (impression cytology) in 165 eyes from 85 patients with primary Sjögren's syndrome and in 80 eyes from 40 control subjects. Impression cytology can provide the location of cellular alterations on the ocular surface and information on the severity of the disease. The upper bulbar and interpalpebral areas from patients with primary Sjögren's syndrome were shown to have cellular alterations early in the course of the disease, while the lower bulbar and lower palpebral areas were only affected in severe cases. Statistical analysis has shown that impression cytology and rose bengal staining are the most specific and sensitive methods for the diagnosis of primary Sjögren's syndrome.

Topics: Adult; Aged; Aged, 80 and over; Conjunctiva; Epithelium; Female; Humans; Lactoferrin; Male; Middle Aged; Muramidase; Reproducibility of Results; Rose Bengal; Sensitivity and Specificity; Sjogren's Syndrome; Staining and Labeling; Tears

Unstimulated saliva was fractionated by micro two-dimensional gel electrophoresis, and the proteins visualized by silver staining and immunostaining. The subjects with Sjögren's syndrome exhibited both quantitative and qualitative alterations in the protein composition of the saliva not only from the parotid gland but also from the submandibular/sublingual glands.

Topics: Albumins; alpha-Amylases; Case-Control Studies; Diabetes Mellitus, Type 1; Electrophoresis, Gel, Two-Dimensional; Female; Humans; Immunoglobulin A, Secretory; Immunoglobulin G; Lactoferrin; Male; Middle Aged; Parotitis; Salivary Proteins and Peptides; Sialadenitis; Sjogren's Syndrome

In search of a simple non-invasive diagnostic test for primary Sjögren's syndrome (SS) the concentration of beta 2-microglobulin (beta 2-m), lysozyme (LZM) and lactoferrin (Lf) was measured in stimulated parotid saliva of 39 patients with primary SS, 42 patients suspected of the syndrome in whom the diagnosis could be excluded (NON-SS) and in 41 normal control individuals. Salivary fluid levels of beta 2-m, LZM and Lf exceeding the mean + 2 x standard deviation of healthy control values were found in respectively 58%, 23%, and 26% of the primary SS patients and in 7%, 11% and 0% of the NON-SS patients. The results of this study indicate that due to the low sensitivity the tests are not suitable as a screening procedure for patients suspected of having primary SS. However, measurement of beta 2-m in stimulated parotid saliva may be used as an adjunctive diagnostic test for primary SS.

Topics: Adult; Aged; Aged, 80 and over; beta 2-Microglobulin; Female; Humans; Lactoferrin; Male; Middle Aged; Muramidase; Osmolar Concentration; Reference Values; Saliva; Sjogren's Syndrome

The concentrations of sodium, potassium, calcium, protein and lactoferrin and the enzymatic activity of salivary kallikrein, phosphohexoisomerase, alpha-amylase, lysozyme and IgA were measured in the parotid saliva of 12 patients suffering from Sjögren's syndrome. Compared with a control group (n = 31) remarkable differences were found in the composition of the parotid saliva in Sjögren patients. The possible reasons for these sialochemical alterations are discussed.

Topics: Adult; Amylases; Electrolytes; Glucose-6-Phosphate Isomerase; Humans; Immunoglobulin A, Secretory; Kallikreins; Lactoferrin; Middle Aged; Muramidase; Saliva; Salivary Proteins and Peptides; Salivation; Secretory Rate; Sjogren's Syndrome

In a group of patients with keratoconjunctivitis sicca (KCS) associated with Sjögren's syndrome (SJ) a significant decrease in tear fluid lactoferrin concentration and tear film break-up time was demonstrated in comparison with a matched group in which KCS was not associated with any systemic disease. The Schirmer values were also lower in the SJ of patients and these differences almost reached statistical significance. None of these parameters in itself appeared to be of any clinical value to differentiate between KCS that was or was not associated with SJ. The combination of the tear fluid lactoferrin concentration, the Schirmer I test values and the tear film break-up time, however, provide a basis for differential diagnosis that is clinically of some value.

Topics: Adult; Aged; Aged, 80 and over; Humans; Keratoconjunctivitis; Keratoconjunctivitis Sicca; Lactoferrin; Middle Aged; Osmolar Concentration; Proteins; Sjogren's Syndrome; Statistics as Topic; Tears

Topics: Antibodies, Monoclonal; Gastric Mucosa; Histocytochemistry; Humans; Immunohistochemistry; Lactoferrin; Leukocytes, Mononuclear; Lichen Planus; Lupus Erythematosus, Systemic; Mouth Diseases; Salivary Glands; Salivary Glands, Minor; Sjogren's Syndrome; T-Lymphocytes

Topics: Adult; Aged; Female; Humans; Immunoenzyme Techniques; Lactoferrin; Lactoglobulins; Middle Aged; Radioimmunoassay; Saliva; Salivary Glands; Sjogren's Syndrome

Lactoferrin is present in pancreatic juice, and greatly increased concentrations are found in the pancreatic juice of patients with chronic pancreatitis. It is not known whether these high levels of lactoferrin represent a genetically determined defect predisposing to the later development of chronic pancreatitis or are simply a consequence of the disease. In view of the morphological and functional similarities between the pancreatic and parotid glands, we have measured the immunoreactive lactoferrin concentration in pure parotid saliva of 30 patients with chronic calcific pancreatitis, 26 controls, 5 patients with proven pancreatic cancer, 2 patients with Sjögren's disease and 2 patients with chronic recurrent parotitis. No difference in the lactoferrin concentration was detected between control subjects and patients with chronic pancreatitis or pancreatic cancer. Raised levels were found in the 4 patients with parotid gland disease. These findings suggest that increased lactoferrin secretion is confined to the exocrine pancreas in patients with chronic pancreatitis and is thus probably a phenomenon secondary to the disease.

Topics: Calcinosis; Chronic Disease; Humans; Lactoferrin; Lactoglobulins; Pancreatic Neoplasms; Pancreatitis; Parotid Gland; Parotitis; Radioimmunoassay; Saliva; Sjogren's Syndrome; Specimen Handling

During the active phase of chronic recurrent parotitis there is a marked elevation in the parotid concentration of lactoferrin (Lf), and iron-binding glycoprotein with antibacterial properties. The Lf concentration decreases during the recovery period, but still remains above normal levels. The changes of Lf in parotitis parallel recent findings in mastitis and pancreatitis. Elevations in Lf were also noted in five of six subjects with Sjögren's disease, but not in subjects with sarcoidosis, diabetes or "dry mouth" without sialographic changes. The source of the Lf has not been determined; it could arise in part from disrupting polymorphonuclear leucocytes and in part from epithelial cells that synthesize Lf in the salivary glands. Inflammatory stimulation of Lf synthesis would suggest a basic protective mechanism in exocrine glands and should be fully explored.

Topics: Albumins; Chronic Disease; Diabetes Mellitus; Humans; Lactoferrin; Lactoglobulins; Parotitis; Recurrence; Saliva; Sarcoidosis; Secretory Rate; Sjogren's Syndrome; Xerostomia