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ID PMID Title PublicationDate abstract
9431589 Saliva: an additional diagnostic tool in Sjögren's syndrome. 1997 Dec OBJECTIVE: To assess the available data and the place of salivary analysis in the diagnosis of Sjögren's syndrome (SS). METHODS: 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. RESULTS: 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. CONCLUSION: 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.
9197558 Tear fluid plasmin activity of dry eye patients with Sjögren's syndrome. 1997 Apr Thirty-two eyes of 16 patients with verified Sjögren's syndrome were examined for clinical signs of dry eye. Tear fluid samples were collected for plasmin assay. Ophthalmologic examinations included estimation of conjunctival or corneal discharge, filament formation and presence of conjunctival or corneal epithelial defects, assessment of tear meniscus height and measurement of tear fluid break-up time, Schirmer test, and fluorescein and Rose-Bengal staining graded by the van Bijsterveld score. Tear fluid plasmin activity (IU/l) was determined by a fluorometric assay and tear fluid flow (microl/min) was measured for calculation of tear fluid plasmin activity release (microIU/min). All patients had relatively dry eyes; the mean Schirmer test value was 5.7 +/- 0.5 mm/5 min. The mean tear fluid break-up time was also low, 7.7 +/- 0.5 s. The mean Bijsterveld score value was 2.5 +/- 0.5. Because collection of tear fluid by microcapillaries for the plasmin assay was difficult due to the low tear fluid flow rate, it was necessary to drop 20 microl of balanced salt solution topically on the cornea to aspirate a tear fluid sample. Despite this, the mean tear fluid plasmin activity was higher than in control individuals (7.75 +/- 1.51 IU/l vs. 0.73, range 0.64-0.80 IU/l). On the basis of these findings we conclude that elevated tear fluid proteolytic activity may play a role in the pathology of dry eye/ocular surface disease.
11708433 Sjögren's syndrome associated T cell large granular lymphocyte leukemia: a possible commo 2001 Nov Two patients with primary Sjögren's syndrome and T cell large granular lymphocyte (LGL) leukemia are described. One patient had evidence of T cell LGL salivary gland infiltration, suggesting a possible common etiopathogenesis for these 2 conditions.
11699983 Salivary enhancement: current status and future therapies. 2001 Oct Saliva provides the principal protective milieu for teeth by modulating oral microbial ecosystems and reversing the initial phases of caries development. Patients with inadequate salivary function are at increased risk for dental decay. Therefore, it is likely that therapies that increase overall fluid output of these individuals will reverse early carious lesions. The most common causes of salivary dysfunction are medication usage, Sjögren's syndrome, and damage of salivary parenchyma during therapeutic irradiation. For patients with remaining functional acinar tissue, treatment with the parasypathomimetic secretogogues pilocarpine and Cevimeline may provide relief. However, these medications do not benefit all patients. The possibilities of using gene therapy and tissue engineering to develop treatments for those with severe salivary dysfunction are discussed.
11530996 Can B cell epitopes of 60 kDa Ro distinguish systemic lupus erythematosus from Sjögren's 2001 Antibodies binding components of the Ro/La (or SSA/SSB) ribonucleoprotein particle are found in the sera of patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) as well as mothers who give birth to babies with neonatal lupus. Anti-La occurs in a subset of sera that contain anti-Ro, and anti-La is found more commonly in sera of patients with SS than in sera from SLE patients. The fine specificity of autoantibodies binding 60 kDa has been studied extensively. Recent data have suggested that there are disease-specific epitopes which identify patients with either SLE or SS. Alternatively, other data suggest that the B cell epitopes of 60kDa Ro vary according to the presence of anti-La. The present study was undertaken to determine whether binding of putative disease-specific 60 kDa Ro epitopes is associated with the diagnosis of SLE vs SS, or instead associated with the presence of anti-La. Anti-60 kDa Ro positive sera from 24 SLE patients and 44 SS patients were studied for antibodies binding two epitopes of 60 kDa Ro. We find the epitope defined by residues 171-190 is associated with anti-60 kDa Ro without anti-La, regardless of diagnosis. Meanwhile, binding of the epitope defined by residues 215-232 is not commonly found in anti-60 kDa Ro sera, especially in those sera with both anti-60 kDa Ro and anti-La. Thus, the fine specificity of antibody binding to 60 kDa Ro varies according to the presence of anti-La, not to the diagnosis of either SLE or SS.
11296454 [A case of Sjögren's syndrome with dermatomyositis who died of rapidly progressive inters 2001 Feb We report a case of 55 year-old woman with six year history of Sjögren's syndrome developed fatal rapidly progressive interstitial pneumonia. She had been well until February 1999. She developed swelling and erythematous lesions in the cheek and hands in spring 1999. She was admitted to our hospital for investigations of skin lesions in May 1999. Physical examination on admission revealed small hemorrhagic lesions in the nailfold. Serum CK level was slightly elevated. Electromyogram and MRI suggested mild myositis in the proximal upper extremities. She was suspected to have dermatomyositis along with Sjögren's syndrome. Prednisolone 10 mg/day had been given for her skin problems since March 1999. Suddenly, dyspnea on exertion was appeared on 34th day of admission. Chest X-ray film showed an acute worsening of interstitial pneumonia. Methylprednisolone pulse therapy (1000 mg for 3 days) and cyclophosphamide pulse therapy (500 mg for a day) were started, and she was subsequently treated with 60 mg/day of prednisolone and 250 mg/day of Cyclosporin A. However, interstitial pneumonia did not respond to the treatment, and pneumomediastinum and pneumothorax have developed. She died of respiratory failure on 55th day. We consider that most likely explanation for fatal interstitial pneumonia is concomitantly occurred dermatomyositis.
11129549 [Salivary gland scintigraphy en Sjogren syndrome and its relation with the result of lip b 2000 Aug BACKGROUND: Salivary gland scintigraphy allows a non invasive, morphological and functional assessment of parotid and submaxillary salivary glands. AIM: To describe the main features of salivary gland scintigraphy in patients with Sjögren syndrome, rheumatic fibromyalgia and normal controls and compare the results with lip biopsy. PATIENTS AND METHODS: Sixty one normal controls, 66 patients with Sjögren syndrome and 18 patients with rheumatic fibromyalgia were studied. For the diagnosis of Sjögren syndrome and fibromyalgia rheumatica, the Modified European and American College of Rheumatology criteria were used, respectively. Lip biopsies were obtained in 52 patients with Sjögren syndrome. Scintigraphy was done with a gamma camera and computer after the administration of 99mTc-pertechnetate, obtaining images during 30 min and creating time/activity curves. Scintigraphy was classified as normal, with mild or severe alterations. RESULTS: Scintigraphy was normal in 74% of control subjects and in 26%, it had mild alterations. In 72% of patients with rheumatic fibromyalgia, scintigraphy was normal whereas in 28%, it had mild alterations. In 27% of patients with Sjögren syndrome, scintigraphy was normal, in 27% it had mild alterations and in 46%, severe alterations. There was a positive and significant correlation between pathological alterations of salivary glands and scintigraphic alterations (r = 0.642, p < 0.001). CONCLUSIONS: Severe scintigraphic alterations of salivary glands strongly support the diagnosis of Sjögren syndrome. Mild alterations are non specific and a normal scintigraphy does not exclude the diagnosis.
10954994 Sjögren's syndrome and granulomatous panniculitis. 2000 Aug An 83-year-old Cambodian woman presented with multiple painful erythematous nodules on the lower legs, forearms and wrists. Subsequent history and investigations revealed a granulomatous lobular panniculitis associated with Sjögren's syndrome. This is a rare cutaneous association of Sjögrens syndrome with only three similar case reports in the literature.
10954475 MR imaging of the salivary glands in sicca syndrome: comparison of lipid profiles and imag 2000 Sep OBJECTIVE: We correlated abnormalities on MR imaging with the plasma lipid profiles of patients with hyperlipidemia and symptoms of sicca syndrome. SUBJECTS AND METHODS: MR imaging features of the salivary glands, salivary function, immunologic abnormalities, and plasma lipid profiles were analyzed in 24 patients with hyperlipidemia and symptoms of sicca syndrome and compared with those of 50 patients with Sjögren's syndrome. RESULTS: Swelling of the parotid gland, impaired salivary flow, or both were observed in 20 (83%) of 24 patients with hyperlipidemia and symptoms of sicca syndrome. MR imaging findings included an enlarged parotid gland replaced with extensive lipid infiltration, whereas sialography of the parotid gland revealed normal findings. Immunologic studies and analyses of the labial glands of the mouth revealed distinctive features in patients with Sjögren's syndrome. Importantly, elevated levels of plasma triglyceride correlated with parotid gland swelling, and increased cholesterol levels significantly affected salivary flow. CONCLUSION: Our findings suggest a distinct entity of sicca syndrome in patients with hyperlipidemia compared with patients with Sjögren's syndrome. Characteristic MR imaging findings of salivary glands in patients with hyperlipidemia included extensive lipid infiltration and gland enlargement.
10376080 Detecting anti-SSA and anti-SSB antibodies in routine analysis: a comparison between doubl 1999 May The aim of this study was to assess the performance of a commercially available procedure for detecting anti-Sjögren's syndrome A (anti-SSA) and anti-Sjögren's syndrome B (anti-SSB) antibodies by immunoblotting (IB) and compare it with double immunodiffusion (DID). We also studied the clinical significance of these profiles in a series of unselected anti-SSA positive patients. Serum samples from 534 patients that were positive on an immunofluorescent screening test using HEp-2 cells were analysed for anti-SSA and anti-SSB antibodies by DID and IB (Biolab Anablot System II), and the results on anti-SSA antibodies were confirmed by an enzyme-linked immunosorbent assay (ELISA). Fifty-five serum samples were found to be positive for anti-SSA antibodies. Among these, 24 were anti-SSA negative by IB but positive by DID and ELISA ('non-blotter sera'), whereas only three serum samples were anti-SSA negative by DID but positive by IB and ELISA. Of the 18 anti-SSB positive serum samples, eight were negative by DID. All the serum samples that were anti-SSB positive by DID were also positive by IB. Anti-SSB antibodies showed a significant association with eye dryness and leucopenia. Anti-52 kDa SSA antibodies were associated with anti-SSB antibodies but showed no significant association with sicca symptoms, while anti-60 kDa SSA antibodies were associated with lower rates of leucopenia. The 'non-blotter' profile showed no significant association with any clinical parameter. IB is less sensitive than DID for detecting anti-SSA antibodies but more sensitive than DID for detecting anti-SSB antibodies. The determination of anti-SSA immunoblotting profiles in patients positive for anti-SSA antibodies by DID does not significantly improve the clinical usefulness of this test. As expected, anti-SSB antibodies were associated with clinical features of Sjögren's disease. Non-blotting (probably conformational) anti-SSA antibodies did not show any further association with clinical parameters and seem to have no clinical relevance.
9870881 Detection of anti-Ro/SSA and anti-La/SSB autoantibody-producing cells in salivary glands f 1998 Dec OBJECTIVE: To investigate and identify the presence of cells producing anti-Ro/SSA and anti-La/SSB autoantibodies in salivary glands from patients with Sjögren's syndrome (SS). METHODS: Submucosal salivary gland biopsy samples from 10 SS patients (8 with and 2 without circulating Ro and La autoantibodies) and 14 control subjects were evaluated. Frozen tissue sections were immunostained by an avidin-biotin complex technique, using biotinylated recombinant Ro and La proteins as detection reagents. Autoantibody levels in SS patient sera were analyzed by enzyme-linked immunosorbent assay. RESULTS: Cells producing autoantibodies to the Ro 52-kd, Ro 60-kd, and La proteins were recorded in 8, 6, and 7 of the 10 SS patient biopsy samples, respectively. Samples from the 2 SS patients without circulating Ro and La autoantibodies were negative for these autoantibody-producing cells, as were all control biopsy samples. A strong positive correlation between the presence of autoantibodies in sera and the presence of autoantibody-producing cells in glandular biopsy tissues was evident. The number of autoantibody-producing cells and the serum autoantibody levels were also correlated (r(s)=0.94, P < 0.0001). CONCLUSION: Using a novel technique, we have demonstrated the presence of Ro and La autoantibody-producing cells in salivary gland biopsy tissues from patients with SS. These findings indicate that anti-Ro/ SSA and anti-La/SSB autoantibodies are produced and are present at sites of inflammation and indicate their potential involvement in the autoimmune exocrinopathy of this disease.
9376993 Quantitative assessment of salivary gland inflammatory infiltration in primary Sjögren's 1997 Sep The aim of this study was to investigate the possible relationship between the degree of inflammatory infiltration of salivary glands in Sjögren's syndrome (SS) and the different demographic, clinical and serological features of the disease. A quantitative assessment of the extension of the infiltrates was performed on histology samples from the labial salivary glands (LSG) of 82 patients with primary SS, by calculating the ratio of the infiltrated area to the total area of glandular tissue in the samples. The correlations between the amount of inflammatory infiltrate and the main features of the disorder were then analysed. A significant negative correlation between the degree of LSG infiltration and the patient's age at disease onset was observed (P < 0.05). In contrast, the percentage of infiltrate did not correlate with the disease duration. A significant correlation was found between the degree of infiltration of the salivary tissue and (i) the total number of extraglandular features (P < 0.01) and (ii) the presence of specific extraglandular features such as Raynaud's phenomenon (P < 0.05), vasculitis (P < 0.0001), lymph node or spleen enlargement (P < 0.05) and leucopenia (P < 0.02). Finally, patients with antinuclear antibodies, anti-SSA/Ro antibodies, or anti-SSA/Ro plus anti-SSB/La antibodies showed a more widespread inflammatory infiltration in the LSG tissue than patients without these autoantibodies (P < 0.01). The degree of infiltration in the salivary tissue was significantly greater in those patients with anti-SSA/Ro plus anti-SSB/La antibodies in their sera than in patients with anti-SSA/Ro antibodies alone (P < 0.05). In conclusion, patients with SS and active inflammatory infiltration of the salivary glands usually experience an earlier disease onset and a larger number of systemic extraglandular manifestations. In addition, the antibodies directed against certain nuclear/cytoplasmic specificities, and particularly those which react with the SSB/La antigen, seem to play a key role in enhancing the autoimmune process in the salivary glands.
9195514 Salivary and serum interleukin 6 in primary Sjögren's syndrome. 1997 Jun OBJECTIVE: To measure interleukin 6 (IL-6) salivary and serum concentrations in primary Sjögren's syndrome (SS), to correlate these data with the clinical presentation in patients, and to determine if salivary IL-6 is reflective of local exocrine involvement or of the underlying autoimmune disorder. METHODS: Thirty-one patients with primary SS, 15 with primary biliary cirrhosis (PBC), and 14 healthy controls were studied. Parotid secretion was stimulated with 2% citric acid and collected using a Carlson-Crittenden collector. Concentrations of salivary and serum IL-6 were determined using a high sensitivity ELISA. Serologic autoimmune disease markers and salivary functional and histopathologic disease markers in the patients with SS were correlated with salivary and serum IL-6 levels. RESULTS: Mean serum IL-6 concentrations were elevated in both patient groups (SS = 3.05 pg/ml, PBC = 3.07 pg/ml, healthy subjects = 0.843 pg/ml). Mean stimulated salivary IL-6 concentrations were elevated only in the patients with SS (16.21 pg/ml) compared to the PBC (1.07 pg/ml) and healthy subjects (0.769 pg/ml). No correlation was found between serum and salivary IL-6 concentrations for any group. Positive correlations were found between salivary IL-6 concentrations and serum IgG concentrations and between salivary IL-6 and erythrocyte sedimentation rate. Higher IL-6 concentrations were associated with increased disease activity. CONCLUSION: Salivary IL-6 concentration is elevated in SS compared to healthy subjects and patients with another systemic autoimmune disease without salivary gland involvement. Elevated salivary IL-6 concentrations in SS are reflective of local exocrine involvement and may serve as a useful monitor of disease activity.
9060643 A novel exogenous retrovirus sequence identified in humans. 1997 Apr A 932-bp retrovirus sequence was cloned by reverse transcriptase PCR from salivary gland tissue of a patient with Sjögren's syndrome. The sequence is related to that of type B and type D retroviruses and was present in a sucrose density gradient fraction corresponding to that of an enveloped retrovirus particle. Sequences amplified from tissues of eight individuals with or without Sjögren's syndrome had over 90% similarity and were present at a level of less than one copy per 10(3) cells. The sequence was not detectable in human genomic DNA by PCR or by Southern hybridization. These data indicate that the sequence represents an infectiously acquired genome, provisionally called human retrovirus 5.
9385343 Serological findings in patients with acute syndromes fulfilling the proposed criteria of 1997 In order to analyse possible triggering or contributing infections and HLA-B27 frequency in patients with acute febrile joint syndrome fulfilling the proposed criteria of adult Still's disease (AOSD), we studied prospectively the serological findings of 25 patients. They were aged 15-62 years and diagnosed between 1978-1992. We then compared results with a control group consisting of 119 healthy persons. Positive viral or bacterial serology was found in 12 patients (48%) in the AOSD group compared with 13 cases (11%) in the control group (p < 0.001). Fourfold or higher viral antibody rise was found in two patients and bacterial antibody rise in three patients. High stable viral antibody titre was observed in one patient and high stable bacterial antibody titre in six patients. HLA-B27 was not overrepresented in the study group (12%) compared with a healthy Finnish population (14%). We conclude that many different bacterial and viral infections may trigger or contribute to AOSD.
11853607 [Apoptosis and related gene expression in lacrimal gland of cases with Sjögren's syndrome 2000 Jul OBJECTIVE: To assess the roles of apoptosis and expression of the related genes in lacrimal glandular destruction of patients with Sjögren's syndrome (SS). METHODS: Small pieces of palpebral lobes of lacrimal glands were obtained from 12 patients (10 with primary Sjögren's syndrome, 2 with secondary Sjögren's syndrome) and 7 normal controls. They had been investigated by the in situ end labeling and immunohistochemical staining to detect the apoptotic cells and the expression of Fas, FasL, bcl-2 and Bax. RESULTS: The number of epithelial apoptotic cells in lacrimal glands of patients with SS was significantly higher than that in normal glands, and SS epithelial cells showed increased expression of Fas, FasL and Bax. There was significant positive correlation between the number of the apoptotic cells and that of the cells expressing Fas, FasL and Bax, respectively, and there was significant negative correlation between the number of the apoptotic cells and that of the cells expressing bcl-2. CONCLUSIONS: The apoptosis of the epithelial cells in the lacrimal gland may be one of the mechanisms leading to the glandular destruction found in SS. In SS lacrimal glands, the expression of Fas, FasL and Bax may promote apoptosis, and the expression of bcl-2 may inhibit apoptosis.
11665979 Infliximab in patients with primary Sjögren's syndrome: a pilot study. 2001 Oct OBJECTIVE: Tumor necrosis factor alpha (TNFalpha) is a proinflammatory cytokine involved in the pathogenesis of Sjögren's syndrome (SS), and blockade of TNFalpha may reduce the activity of the disease. The purpose of this study was to evaluate the safety and potential efficacy of infliximab, a chimeric human-mouse anti-TNFalpha monoclonal antibody, in patients with active primary SS. METHODS: This was a single-center, open-label pilot study. Sixteen patients with active primary SS received 3 infusions of infliximab (3 mg/kg) at 0, 2, and 6 weeks. Standard clinical assessment, complete ophthalmologic testing, and functional evaluation of salivary flow were performed at baseline and at weeks 2, 6, 10, and 14. RESULTS: All patients completed the study. There was statistically significant improvement in all clinical and functional parameters, including global assessments (patient's global assessment, patient's assessment of pain and fatigue, physician's global assessment), erythrocyte sedimentation rate, salivary flow rate, the Schirmer I test, tender joint count, fatigue score, and dry eyes and dry mouth. This clinical benefit was observed at week 2 and was maintained throughout the study and the 2-month followup period. The treatment was well tolerated in all patients, and no significant adverse events were seen. No lupus-like syndrome was observed, and no anti-double-stranded DNA antibodies were observed that were attributable to infliximab therapy. CONCLUSION: In patients with active primary SS, a loading-dose regimen of 3 infusions of infliximab provided a fast and significant clinical benefit without major adverse reactions. It was possible to maintain statistically significant improvement for up to 8 weeks after the third infusion.
11014971 Sjögren's syndrome: autoantibodies to cellular antigens. Clinical and molecular aspects. 2000 Sep Autoantibodies to cellular autoantigens are usually found in sera of patients with systemic autoimmune rheumatic diseases. Patients with Sjögren's syndrome (SS) frequently present autoantibodies to both organ and non-organ-specific autoantigens. The most commonly detected autoantibodies are those directed against the ribonucleoproteins Ro/SSA and La/SSB. The presence of the antibodies in SS is associated with early disease onset, longer disease duration, parotid gland enlargement, higher frequency of extraglandular manifestations and more intense lymphocytic infiltration of the minor salivary glands. Over the past several years, the structure and function of these autoantigens have been extensively studied. Several centers, using different techniques, have investigated the B cell epitopes on the protein components Ro 60 kD, Ro 52kD, and La 48 kD. Finally, increased evidence of direct involvement of anti-Ro/SSA and anti-La/SSB autoantibodies in the pathogenesis of tissue injury has been contributed by several studies.
10469404 An autopsy case of primary nodal plasmacytoma associated with Sjögren's syndrome. 1999 Jun An 81-year-old man with a 1 year history of Sjögren's syndrome and hypergammaglobulinemic purpura was admitted because of high fever and lymphadenopathy. Primary nodal plasmacytoma was suggested from the microscopic and immunohistochemical findings of an inguinal lymph node biopsy specimen. Although chemotherapy achieved a moderate response, the patient died 2 months later from respiratory and cardiac failure. We herein, is described a rare autopsy case of primary nodal plasmacytoma associated with Sjögren's syndrome, in which the clinical course was progressive and Epstein-Barr virus-encoded RNA 1 was positive in a small number of neoplastic plasma cells, showing some difference from previously reported cases.
9558170 Decreased Fcgamma receptor III (CD16) expression on peripheral blood mononuclear cells in 1998 Apr OBJECTIVE: To examine the expression of surface structures important in natural killer (NK) cell function and the roles of serum factors affecting the expression of surface antigens on these cells in patients with Sjögren's syndrome (SS). METHODS: Peripheral blood mononuclear cells (PBMC) of 18 patients with SS were analyzed by immunofluorescence on a flow cytometer. The antigen recognized by autoantibodies in their sera was analyzed by immunofluorescence and by immunoprecipitation. RESULTS: Expression of Fcgamma receptor III (CD16), an important indicator of NK cytolytic activity, on PBMC was significantly decreased in patients with SS who have extraglandular disease, while the expression of Fcgamma RI and II was normal. Moreover, F(ab')2 of IgG in these patients' sera was shown to bind to CD16+ cells. Immunoprecipitation study showed that it bound to CD16 itself. CONCLUSION: The depressed expression of CD16 on PBMC and the presence of antibody binding to CD16 in the patients' sera may be, at least in part, responsible for the altered function of NK cells observed in SS.