bromochloroacetic-acid and Sjogren-s-Syndrome

Significant progress in the diagnosis and therapy of salivary gland diseases has been made in recent years. The new technique of diagnostic and interventional sialendoscopy has made an important contribution and is indicated in every case of obstructive sialadenitis. The number of open resections of salivary glands due to stones will clearly decrease in the future in favor of endoscopic removal. Due to recent publications on the appropriate extent of salivary gland resection in benign tumors, more and more specimens with reduced cuffs of healthy salivary gland tissue will be sent to the pathologists. Ultrasound will stay the procedure of first choice for imaging of salivary gland diseases in Germany. In combination with fine-needle aspiration cytology high sensitivity and specificity for the assessment of salivary gland tumors can be achieved. Diffusion-weighted magnetic resonance imaging (MRI) is a new imaging tool and the power of distinction of pleomorphic adenoma from malignant tumors is promising. The use of botulinum toxin for salivary glands diseases is increasing. Intraglandular injections have been shown to induce salivary gland atrophy in animal experiments. The availability of biologicals is currently yielding new aspects for the treatment of Sjögren's disease.

Topics: AIDS-Related Opportunistic Infections; Biomarkers, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; Cysts; Diagnosis, Differential; Epithelium; Humans; Keratins; Lymph Nodes; Lymphoma, B-Cell, Marginal Zone; Parotid Diseases; Salivary Ducts; Salivary Gland Neoplasms; Salivary Glands; Sialadenitis; Sjogren's Syndrome

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 investigate the Raman spectral characteristics of the pathological lip minor salivary glands affected in primary Sjögren's syndrome.. Thirty pathological samples and 30 normal samples were collected in this study. The samples were examined by Raman microscope.Support vector machine(SVM) was employed to analyze the data and establish the classification model.. The spectra of pathological tissues was different from the controls in proteins, nucleic acids, lipids and glycogen skeleton. The sensitivity, specificity and accuracy of the model established by SVM on the training sets were all 92.0% (92/100), but the sensitivity, specificity and accuracy of the model established by SVM on the testing sets were 69.2% (37/53), 100.0% (37/37) and 82.0% (73/89) respectively.. There was significant difference in Raman spectra between the pathological and normal lip salivary glands, and the classification model established by SVM could discriminate the pathological glands from the normal ones.

Topics: Female; Glycogen; Humans; Keratins; Lip; Lipids; Male; Middle Aged; Nucleic Acids; Salivary Glands, Minor; Sjogren's Syndrome; Spectrum Analysis, Raman

Primary Sjögren's syndrome (pSs) is an autoimmune rheumatic disease that may express in a small number of patients a spectrum of lymphoproliferative diseases. The aim of this study was to describe clinical, imaging and pathology features of the extranodal marginal zone B-cell lymphoma (MZCL) of the lung of mucosa-associated lymphoid tissue (MALT) type in patients with pSs.. All patients (N=10) with biopsy proven MZCL of the lung of MALT type diagnosed in a tertiary teaching hospital during the last 7 years were studied.. Seven patients had pSs. Almost all patients presented an indolent clinical course, contrasting strongly with the spectacular radiological findings in both chest roentgenograms and computed tomography. Pathology infiltration patterns observed were either nodular, peribronchial-perivascular, alveolar, or interstitial. Immunohistochemical study in all cases showed B cell phenotypes. Immunoglobulin light chain restriction was demonstrated in all patients. Monoclonal IgM(kappa) was evident in 5/7, IgM(lambda) in 1/7 and IgG (kappa) in 1/7 of patients.. Lung MZCL associated with pSs are characterized by an important dissociation between clinical expression and radiological pattern. Clinical presentation and imaging features are not specific. Therefore, histologic documentation is mandatory to ensure diagnosis. Various chemotherapeutic agents in combination with rituximab lead to partial or complete remission in the majority of patients.

Topics: B-Lymphocytes; Biomarkers; CD4-Positive T-Lymphocytes; Female; Humans; Immunohistochemistry; Keratins; Lung; Lymphoma, B-Cell; Lymphoma, B-Cell, Marginal Zone; Male; Sjogren's Syndrome; Tomography, X-Ray Computed

Our previous gene expression analysis suggested that conjunctival epithelial cells of Sjögren's syndrome (SS) are inclined to hyper-proliferation and keratinisation status. The goal of this study is to elucidate whether such pathological situations really exist in the conjunctival epithelium of SS. Also, involvement of inflammatory cytokines in this disease was investigated. Conjunctival tissues or cells obtained from 12 SS patients and 13 normal subjects were subjected to indirect immunostaining to analyse expression of transglutaminase 1 (TGase1), involucrin, keratins 1, 4, 10 and 13. The number of proliferative cells was also analysed by immunostaining of Ki67 antigen. Additionally, changes in gene expression of TGase1 and involucrin after stimulation by IL-1 or IFN-gamma were quantified by real-time RT-PCR. TGase1 and involucrin were up-regulated in the conjunctival epithelium of SS patients. Although not statistically significant, Ki67 positive proliferative cells were slightly increased in SS patients. IFN-gamma stimulation significantly up-regulated TGase1 and unexpectedly repressed involucrin gene expression. IL-1 did not render any significant changes in the expression of these genes. These results suggest the existence of pathological keratinisation in the conjunctival epithelium of SS and also support our hypothesis that inflammatory cytokines may be involved in the ocular surface pathological changes in SS.

Topics: Aged; Biomarkers; Case-Control Studies; Cell Proliferation; Cells, Cultured; Conjunctiva; Epithelium; Female; Fluorescent Antibody Technique, Indirect; Gene Expression; HLA-DR Antigens; Humans; Interferon-gamma; Interleukin-1; Interleukin-8; Keratins; Middle Aged; Protein Precursors; Reverse Transcriptase Polymerase Chain Reaction; Sjogren's Syndrome; Statistics, Nonparametric; Transglutaminases; Up-Regulation

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

Topics: Cell Differentiation; Female; Humans; Immunohistochemistry; Keratins; Ki-67 Antigen; Membrane Proteins; Middle Aged; Protein Precursors; Sjogren's Syndrome; Skin Diseases

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

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 elucidate the pathogenesis of ocular surface abnormalities in patients with Sjögren's syndrome (SS) by comparing global gene expression patterns in conjunctival epithelial cells from normal individuals and SS patients.. The study population consisted of 56 subjects (26 SS patients and 30 normal volunteers). RNA extracted from their conjunctival epithelial cells was subjected to introduced amplified fragment length polymorphism (iAFLP), a competitive PCR-based gene expression assay, to measure gene expression in the 56 samples against 931 genes. Data were analyzed by two-dimensional clustering analysis and discriminant analysis. Disease-related genes were identified and the feasibility of gene expression-based diagnosis of SS was examined.. Two-dimensional clustering- and discriminant analysis clearly distinguished between SS patients and normal subjects. Of 931 genes tested, 34 were significantly up-regulated and 12 were significantly down-regulated in SS (p<0.05). Up-regulated genes included kallikrein 7 (x 15.8) and small proline-rich protein 2A (x 9.6), markers for the terminal differentiation of epidermis, and the inflammation-related genes HLA-DR and IL-6. Monokine-induced-by-gamma-interferon, i.e. c-fos, fibronectin, amphiregulin, defensin beta 2, and keratin 16, -6b and -6c were also up-regulated. Among the 12 down-regulated genes, interferon-gamma receptor 1 was most notable (x1/27.3).. The up-regulated expression of keratin 6 and -16, small proline-rich protein 2A, and kallikrein 7 in the conjunctival epithelium of SS patients suggests an anomalous keratinization pattern. Epithelial thickening may be due to amphiregulin and/or c-fos-stimulated cell cycle progression. The up-regulation of monokine-induced-by-gamma-interferon, HLA-DR, keratin 6b, -6c, and -16 suggests that in SS, interferon-gamma may play an important role in the altered gene expression in the conjunctival epithelium.

Topics: Aged; Amphiregulin; beta-Defensins; Case-Control Studies; Chemokine CXCL9; Chemokines, CXC; Cluster Analysis; Conjunctiva; Cornified Envelope Proline-Rich Proteins; Discriminant Analysis; EGF Family of Proteins; Epithelial Cells; Feasibility Studies; Female; Fibronectins; Gene Expression Regulation; Genes, fos; Genetic Markers; Glycoproteins; Humans; Intercellular Signaling Peptides and Proteins; Kallikreins; Keratins; Male; Membrane Proteins; Middle Aged; Polymerase Chain Reaction; Protein Precursors; Proteins; Sjogren's Syndrome

It is not clear, whether the so-called basal cells of the salivary striated ducts are an independent cell-type distinct from myoepithelial cells, making characterization of the cell proliferation typical of the duct lesions in Sjögren-type sialadenitis/benign lymphoepithelial lesion (BLEL) difficult. An immunohistochemical investigation including different cytokeratin subtypes, alpha-actin, Ki-67 and Bcl-2 was directed at the epithelial cytoskeleton in normal parotid parenchyma (n=8), BLEL (n=12), HIV-associated lymphoepithelial cysts (n=8) and palatine tonsils (n=8). There are profound morphological and functional differences between basal and myoepithelial cells in the normal salivary duct. Development of duct lesions in BLEL arises from basal cell hyperplasia of striated ducts with aberrant differentiation into a multi-layered and reticulated epithelium, characterized by profound alteration of the cytokeratin pattern. This functionally inferior, metaplastic epithelium is similar to the lymphoepithelial crypt epithelium of palatine tonsils. The often postulated participation of myoepithelial cells in duct lesions of Sjögren disease/BLEL cannot be supported. We regard the designations lymphoepithelial lesion and lymphoepithelial metaplasia as the most appropriate.

Topics: Adolescent; Adult; Aged; Biomarkers; Cytoskeleton; Epithelial Cells; Female; HIV Infections; Humans; Hyperplasia; Immunoenzyme Techniques; Keratins; Lymphocele; Male; Middle Aged; Palatine Tonsil; Parotid Diseases; Parotid Gland; Salivary Ducts; Sialadenitis; Sjogren's Syndrome

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

Topics: Actins; Biomarkers; Collagen; Cysts; HIV Infections; Humans; Keratins; Lymphoid Tissue; Sialadenitis; Sjogren's Syndrome

In order to determine which components of the salivary duct cells are recognized by the antisalivary duct antibodies, sera of patients with Sjögren's syndrome were screened for immunoreactivity to keratin by using an ELISA test and a Western blot analysis. The autoantibodies which reacted with keratin were demonstrated in 8 of 9 definite cases of Sjögren's syndrome and in 3 of 6 probable cases, and they reacted with different keratin peptides in each case. The results suggest that the antisalivary duct antibodies include antibodies against keratin, which exists ubiquitously as a cytoskeleton in the salivary gland epithelial cells. Detection of antikeratin antibody might be a useful aid for diagnosis of Sjögren's syndrome.

Topics: Adult; Aged; Autoantibodies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoblotting; Keratins; Middle Aged; Salivary Glands; Sjogren's Syndrome

To determine whether there are specific cytologic features associated with primary Sjögren's syndrome (SS), the authors evaluated impression cytology specimens from three conjunctival sites (temporal bulbar [TB], inferior bulbar [IB], and inferior tarsal [IT]) from 38 SS eyes, 34 eyes of aqueous tear-deficient patients without SS, 35 eyes of seborrheic blepharitis patients, and 17 eyes of normal controls in a masked fashion. The following features were observed more frequently in SS eyes than in the eyes of the other groups: squamous metaplasia of the TB and IB (P less than 0.05), extensive (greater than 75%) goblet cell loss of the TB (P less than 0.05), mucous aggregates of the bulbar conjunctiva (P less than 0.05), and inflammatory cells intercalated with epithelial cells on the IT conjunctiva (P less than 0.06). The conjunctival inflammatory cell infiltrate correlated with the presence of extensive squamous metaplasia (P less than 0.01) in SS specimens. The inflammatory cells on the IT conjunctival epithelium were found to consist predominantly of T-lymphocytes by immunofluorescent staining of cytologic specimens from six eyes. Based on these findings, the authors speculated that conjunctival squamous metaplasia, in addition to aqueous tear deficiency, may be due to primary involvement of the dysfunctional immune system of SS.

Topics: Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, T-Lymphocyte; Blepharitis; CD3 Complex; Cell Adhesion Molecules; Chi-Square Distribution; Conjunctiva; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Lacrimal Apparatus Diseases; Lectins; Receptors, Antigen, T-Cell; Reproducibility of Results; Sialic Acid Binding Ig-like Lectin 2; Sjogren's Syndrome; T-Lymphocytes

The immunoreactivity pattern for different monoclonal antibodies to cytokeratins and to vimentin in epimyoepithelial islands typical for glands of patients with Sjögren's syndrome has been compared with that of normal parotid gland tissue. Two types of epithelial island cells were observed: one had an intermediate filament protein pattern similar to that of ordinary duct epithelial cells of normal parotid gland. The other had an intermediate filament protein pattern typical of myoepithelial and/or basal duct cells in normal glands. Thus, we conclude that the islands are composed of a mixed population of gland cells on the basis of their content of cytokeratins or of cytokeratins and vimentin. These cells might originate from pluripotential reserve cells or from ordinary duct, myoepithelial and/or basal duct cells which may have undergone metaplasia.

Topics: Antibodies, Monoclonal; Epithelium; Fibroblasts; Humans; Immunohistochemistry; Keratins; Parotid Gland; Salivary Gland Diseases; Sialadenitis; Sjogren's Syndrome; Staining and Labeling; T-Lymphocytes; Vimentin

A panel of antibodies has been used in an immunoenzyme study in an attempt to characterize the cell types found in the 'epimyoepithelial' islands of lymphoepithelial lesions. Myoepithelial cells, which can be specifically stained with an anti-smooth muscle antibody were not found. The majority of cells stained with anti-prekeratin, suggesting a duct cell differentiation. A subpopulation of duct cells stainable with a monoclonal antikeratin (16a), previously described as occupying a basal location in normal salivary gland ducts, was clearly demonstrated. It is suggested that these cells may be important in the epithelial proliferation in these islands. The hyaline material within and surrounding the epithelial islands was positive for type IV collagen and therefore consists of basement membrane material.

Topics: Collagen; Epithelium; Histocytochemistry; Humans; Immunochemistry; Keratins; Lymphatic System; Myosins; Parotid Gland; Sjogren's Syndrome

The histogenetic origin of cells in the epimyoepithelial islands occurring in patients with Sjoegren's syndrome has been investigated by using different monoclonal antibodies. The majority of cells in these islands reacted with broad specificity antibodies against keratins. The same cells are stained by a monoclonal antibody CKB1 which detects myoepithelial (basket) cells and basal cells (around the ducts) in normal salivary gland tissue, but which does not stain ductal epithelial cells. Conversely, the cells are not stained by the antibody CK5 which stains ductal epithelial cells in normal salivary gland tissue. The relation of the epimyoepithelial islands to the myoepithelial/basal cell system is thus demonstrated. Certain implications for practical use in surgical pathology are discussed.

Topics: Aged; Antibodies, Monoclonal; Epithelium; Female; Histocytochemistry; Humans; Keratins; Middle Aged; Salivary Glands; Sjogren's Syndrome

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

Immunohistochemistry of salivary gland suggested that keratin is a specific marker of duct-epithelial cells and myosin for myoepithelial cells. Epi-myoepithelial islands found in some autoimmune sialadenitis, such as Sjögren's syndrome, were mainly composed of keratin-positive cells. Keratin filaments, with bundles and desmosome-attachments were invariably found in epithelial cells with electron microscopy. The islands contained no cells with myoepithelial characteristics. The findings show that there is no obvious participation of myoepithelial cells in the growth of the epi-myoepithelial islands.

Topics: Cytoskeleton; Epithelium; Humans; Immunoenzyme Techniques; Keratins; Microscopy, Electron; Salivary Glands; Sjogren's Syndrome