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ID PMID Title PublicationDate abstract
9233605 High affinity rheumatoid factor transgenic B cells are eliminated in normal mice. 1997 Aug 1 Although systemic autoimmune diseases can be accompanied by multiple autoantibodies, certain specificities are dominant. Presumably, these specificities and their cognate Ags have properties that make them particularly amenable to autoimmune induction. Rheumatoid factors (RFs) are a dominant class of autoantibodies in rheumatoid arthritis and certain other autoimmune syndromes. To study the regulation of RFs in normal and autoimmune animals, we previously created a RF Ig transgenic model based on an RF isolated from an autoimmune MRL/lpr mouse. Using this model, called AM14, we were surprised to find that normal mice do not regulate disease-related RF B cells. This raised the question of whether RFs in general are not susceptible to tolerance induction, perhaps due to the unique properties of serum IgG and its FcRs. Alternatively, RFs can be tolerized, and the disease-related RFs are below the affinity threshold for such tolerance. To distinguish these possibilities, we generated a second RF transgenic model with the same specificity but much higher affinity than AM14. We found that, in contrast to AM14, high affinity RF B cells are subject to central tolerance, showing that there is not an absolute defect in RF B cell tolerance, but, rather, that RF B cell tolerance is affinity dependent even in normal animals. This is also the first model in which a disease-related specificity has been shown clearly to delete in a system in which Ag-positive and negative mice can be produced and compared.
11149716 Xerostomia, xerophthalmia, and plasmacytic infiltrates of the salivary glands (Sjögren's- 2001 Jan 1 A 2.5-year-old domestic shorthair cat was evaluated because of dysphagia and weight loss of 4 weeks' duration. MIld blepharospasm and conjunctival hyperemia were evident in both eyes, oral mucous membranes were tacky on palpation, and salivary glands were enlarged. Results of a Schirmer tear test were 0 mm/min for both eyes. Administration of atropine did not cause salivation or caused secretion fo thick rope-like saliva. Examination of biopsy specimens of salivary glands revealed a plasmacytic infiltrate. Sjögren's syndrome (SS) was diagnosed. Oral administration of prednisone was instituted but was discontinued after a minimal positive response was evident 6 weeks after initiation of treatment. Palliative treatment with a 6% solution of pilocarpine 4 to 5 times/d, cyclosporine, hylan A, and neomycin-polymyxin-bacitracin ophthalmic ointment resulted in clinical improvement in the cat. Although reported rarely in animals, SS may be more common than currently is recognized. Most treatment regimens for SS are aimed at alleviating clinical signs.
10514131 Acute self-limiting jejunitis as the first manifestation of microscopic polyangiitis assoc 1999 Aug We report a case of acute self-limiting ulcerative jejunitis of unknown aetiology in a 72-year-old female patient in which a subsequent diagnosis of microscopic polyangiitis and Sjogren's syndrome was made. All known causes of jejunal ulceration and inflammation were excluded. Previously reported cases of acute self-limiting jejunitis are reviewed and the possibility that acute jejunitis in this patient had been the first manifestation of systemic vasculitis is discussed.
10037015 Anaplastic large cell lymphoma associated with Sjögren's syndrome. 1998 Dec We report a case of a 20-year-old Japanese female with recurrent anaplastic large cell lymphoma (ALCL) associated with Sjögren's syndrome (SjS). She was first diagnosed to have ALCL presenting with axillary lymphadenopathy, which within a month underwent spontaneous remission, at the age of 12 years. Eight years later she developed left inguinal lymphadenopathy with clinical overt sicca symptoms associated with elevated serum IgG, interleukin (IL)-1beta and IL-6 levels. Lymph node biopsy was now diagnostic of ALCL characterized by large pleomorphic CD30+ blast cells with the specific chromosomal abnormality, t(2;5)(p23;q35). In contrast to this the salivary gland and renal biopsy revealed infiltration of small lymphocytes, morphologically and cytogenetically distinct from the ALCL cells. Interestingly, SjS symptomatology correlated with disease activity of ALCL and based on an association with elevated IgG and IL-6 levels, suggesting that the concurrence of these two diseases could be more than coincidental. To the best of our knowledge, this is the first reported case of ALCL presenting concurrently with SjS.
9415645 Differential risk of non-Hodgkin's lymphoma in Italian patients with primary Sjögren's sy 1997 Dec OBJECTIVE: To assess the incidence of non-Hodgkin's lymphoma (NHL) and estimate the relative risk (RR) of developing lymphoproliferative complications in a large population of Italian patients with Sjögren's syndrome (SS) and to ascertain if any difference exists between the north and centre-south of Italy. METHODS: Differential relative risks of NHL were obtained by comparing the number of observed cases with cases identified on the basis of age-sex-time specific incidence rates extracted from regional cancer registries. RESULTS: Among the 331 patients with SS studied, 9 cases of NHL occurred, while no lymphoid malignancy appeared in patients with overlapping connective tissue disease (secondary SS) or in males with primary SS. As the number of NHL cases identified on the basis of the rate in the cancer registries would have been 0.27, the RR is 33.3 (p < 0.001). The incidence rate of NHL in Italian patients with SS is about 5.1/1000 person-years. 5.4/1000 per year in the north of the country and 4.8/1000 per year in the centre-south. The relative risks are, respectively, 34.7 and 32.5. CONCLUSION: Italian patients with primary SS have increased risk of developing NHL. In this group, the absence of a significant difference between the north and the centre-south of Italy contrasts with the higher incidence of NHL in the general population of northern regions and strengthens the direct connection between primary SS and NHL.
9272295 Antiphospholipid antibodies in primary Sjögren's syndrome: prevalence and clinical signif 1997 Jul OBJECTIVE: To determine the prevalence and clinical significance of antiphospholipid antibodies (aPL) in a cohort of patients with primary Sjögren's syndrome (SS). METHODS: Eighty patients with primary SS were studied prospectively. The prevalence of aPL and characteristics of the clinical and laboratory features of these patients were compared with those of the following groups of patients: (i) 50 patients with SS associated with systemic lupus erythematosus (SLE); (ii) 100 patients with SLE without SS; and (iii) 100 healthy blood donors from the blood bank of our hospital. RESULTS: Only 11 (14%) patients with primary SS were found to have aPL (anticardiolipin antibodies or lupus anticoagulant, or both) in their sera, but anti beta 2-glycoprotein I antibodies were not detected in any patient. In contrast, aPL were detected in 12 (24%) patients with SS secondary to SLE and in 21 (21%) patients with SLE without SS. None of the healthy controls presented aPL in their sera. Patients with primary SS presented a lower prevalence of thrombocytopenia (p < 0.05) and livedo reticularis (p < 0.01) compared with the other two groups of patients. No patient with primary SS was diagnosed as having an antiphospholipid syndrome (APS), while 4 (8%) patients with secondary SS and 9 (9%) with SLE without SS were found to have APS (p < 0.05). CONCLUSION: In patients with primary SS, aPL are present in a lower percentage than in patients with SS secondary to SLE or in patients with SLE without SS. The presence of aPL in these primary SS patients is not associated with the clinical events of APS.
17657625 Sjögren's syndrome: History, clinical and pathological features. 1998 The history, ocular and oral clinical features, and histopathology of Sjögren's syndrome are described. Primary Sjögren's syndrome is defined when only the ocular and oral components are present, while the secondary form refers to the association with a connective tissue disorder, especially rheumatoid arthritis, or other illness such as AIDS, hepatitis C infection, or biliary cirrhosis. Sjögren's syndrome is a common, but often overlooked disorder. Patients with severe disease run a forty-times risk of developing lymphoma usually of the B cell type.
11320855 [The return of thalidomide]. 2001 Mar Nearly four decades after its withdrawal from the marketplace because of the discover of its teratogenicity, the thalidomide is now attracting a renewed interest due to the identification of its important anti-inflammatory, immunomodulatory and anti-angiogenic effects. After the approval in the United States of the thalidomide for treatment of erythema nodosum leprosum, several studies have been conducted in patients with dermatologic disorders, conditions associated with HIV infection, graft-versus-host disease, rheumatoid arthritis, Cron's disease, and cancer. In this paper the mechanisms of action of thalidomide and its indications in human diseases are summarized.
15775567 [Drug therapy for osteoporosis associated with rheumatoid arthritis (calcitonin)]. 2001 May Calcitonin (CT) inhibits osteoclastic bone resorption and also exhibits long-lasting analgestic action, probably mediating through intrinsic serotonin and opioid peptides. The injection form of eel and salmon CT is only available in Japan. There are a few RCT data regarding the effect of CT on osteoporosis associated with RA, the previous studies have shown its effectiveness in terms of maintaining or increasing bone mineral density in RA patients with or without corticosteroid therapy. RA patients with high turnover osteoporosis and back pain might be a good indication of CT therapy.
11028757 Effect of FTY720, a novel immunosuppressant, on adjuvant-induced arthritis in rats. 2000 Aug OBJECTIVE AND DESIGN: Anti-arthritic effect of FTY720, a novel immunosuppressant, was compared with those of immunosuppressants cyclosporin A and tacrolimus in adjuvant-induced arthritis in rats. MATERIAL: Male LEW rats. TREATMENT: FTY720 (0.03-0.3 mg/kg), cyclosporin A (1-10 mg/kg) or tacrolimus (0.3-3 mg/kg) were orally administered to rats for 21 days beginning on the day (day 0) of adjuvant inoculation. In addition, the anti-arthritic effect of FTY720 (0.3 mg/kg) and cyclosporin A (10 mg/kg) were evaluated by administration to animals for 5 consecutive days (days 2-6, 6-10, and 10-14). METHODS: Adjuvant-induced arthritis was produced by intradermal injection of 0.5 mg heat-killed Mycobacterium tuberculosis. Hindpaw edema was measured plethysmographically. The day of arthritis onset was determined macroscopically. Bone degradation was determined by radiography. Peripheral blood leukocytes were classified microscopically. RESULTS: All test compounds inhibited the incidence of arthritis, hindpaw edema and bone destruction. In addition, FTY720 but not cyclosporin A or tacrolimus markedly decreased the number of peripheral blood lymphocytes. FTY720 treatment on days 6 to 10 inhibited the bone destruction and hindpaw edema. CONCLUSION: These results suggest that the anti-arthritic effect of FTY720 in this adjuvant-induced arthritic model was more potent than those of cyclosporin A and tacrolimus. FTY720 administered on days 6 to 10 showed the inhibitory effect on the bone destruction and hindpaw edema. FTY720 may be effective in the treatment of rheumatoid arthritis.
9416851 Antifibroproliferative effect of tenidap in chronic antigen-induced arthritis. 1997 Dec OBJECTIVE: To determine whether tenidap regulates extracellular matrix metabolism in chronic arthritis. METHODS: Antigen arthritis was induced in the knees of 30 rabbits. Animals were distributed into 3 groups: untreated, tenidap-treated, and diclofenac-treated rabbits. Three weeks after disease induction, synovial membranes were extracted and processed for histopathologic examination and detection of type I collagen (CI) and fibronectin (FN) by immunoperoxidase. Simultaneously, we analyzed the in vitro effect of tenidap on healthy synovial cell (SC) proliferation, FN expression and synthesis, and expression of transforming growth factor beta1 (TGFbeta1) messenger RNA. RESULTS: Untreated animals showed synovial lining hyperplasia, cellular infiltration at the sublining, and increased deposition of matrix proteins. These findings were not apparent in tenidap-treated rabbits, where CI and FN had the same distribution as in healthy synovial membranes. In vitro, tenidap inhibited SC proliferation (> or =25 microM) and down-regulated the expression and synthesis of FN in a dose-dependent manner (> or =1 microM). This antifibrotic effect was associated with a reduction of TGFbeta1 message. CONCLUSION: Tenidap down-regulates the fibroproliferative changes typical of chronic arthritis, an effect that fits the profile of a disease-modifying agent for rheumatoid arthritis.
12476743 [Physical therapy and rehabilitation in rheumatic diseases]. 2001 General principles of physical medicine and rehabilitation of rheumatic diseases are described. In knee and hip osteoarthritis it is important to protect full extension and in evolutive phase treat with drugs, unloading and physical therapy. Rest and ice are efficacious in active rheumatoid arthritis and in chronic phase all procedures and exercises are recommended with respect to pain threshold. Physical therapy for spondy larthropathies is directed to maintenance range of motion exercise for spine and breathing exercises. Swimming is the most appropriate recreational activity for spondylarthropathies.
10734801 Pulmonary epitheloid hemangioendothelioma: a peculiar rare tumor of vascular origin. 2000 Jan An extremely rare case of pulmonary epitheloid hemangioendothelioma (PEH), previously known as intravascular bronchoalveolar tumor (IVBAT), in a 38-year-old female is presented. This patient had a history of rheumatoid arthritis and bilateral multiple small pulmonary nodules which progressed over the years. The histopathological diagnosis of PEH was confirmed by immunohistochemical stains. Prognosis of this tumor is very unpredictable. There is no effective treatment for pulmonary epitheloid hemangioendothelioma.
11887662 Quality of life and nutritional studies in Sjogren's syndrome patients with xerostomia. 2001 Dec People with xerostomia can experience significant difficulties eating some foods which, before the onset of the dry mouth, would have been easily consumed. The few studies in the literature indicate that such people become deficient in a variety of nutrients. In this study, supporting evidence was sought to confirm whether a New Zealand population of people with Sjogren's Syndrome and xerostomia was malnourished. Quality of life issues were measured in the same patients. There was no evidence of nutritional deficiency in the study group, nor did xerostomia seem to be important as a determinant of psychological distress or overall quality of life. As measured by the GHQ-12 score, xerostomic people without their natural teeth were, however, more psychologically distressed than those with a natural dentition. The importance of maintaining the natural dentition in xerostomia is emphasised by this latter result.
11426023 Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of 2001 Jun OBJECTIVES: To determine whether plasma interleukin-6 (IL-6) and G/C base exchange polymorphism at position -174 of the IL6 gene have an effect on the clinical manifestations of primary Sjögren's syndrome (pSS). METHODS: Levels of circulating IL-6 protein and polymorphism of the IL6 gene were analysed in 66 patients with pSS and in 400 healthy subjects. These data were studied in relation to clinical data on the pSS patients. RESULTS: Plasma IL-6 was elevated in pSS patients compared with healthy controls. pSS patients with coeliac disease, pulmonary fibrosis or alveolitis or peripheral nervous system symptoms had significantly higher IL-6 levels than patients without these manifestations. IL-6 levels increased in parallel with the histological grade of minor salivary gland biopsy and the number of pSS criteria fulfilled. IL6 allele frequencies were similar in patients and normal subjects. Plasma IL-6 levels were regulated by the IL6 genotype in pSS patients. CONCLUSIONS: The G/C polymorphism of the IL6 gene does not predispose patients to pSS, but the circulating IL-6 concentration is related to specific manifestations of the disease and the levels of IL-6 are regulated by the IL6 promoter polymorphism in pSS.
9227171 Immunohistochemistry of minor salivary gland biopsy specimens from patients with Sjögren' 1997 Jun OBJECTIVES: To characterise phenotypically the minor salivary glands of patients with clinical and histological features of Sjögren's syndrome (SS) infected with hepatitis C virus (HCV). PATIENTS AND METHODS: 75 consecutive patients with SS (31 primary SS, 44 secondary SS) diagnosed by preliminary European classification criteria. The presence of anti-HCV antibodies was detected by commercial third generation ELISA and by a second generation immunoblot assay. Presence of HCV genome in serum was determined by polymerase chain reaction analysis. Expression of CD3, CD4, CD8, CD20, HLA-DR, and CD25 molecules in lymphocytic and epithelial cells on minor salivary glands was detected by immunohistochemical assays. Expression of interferon gamma and interleukin 4 cytokines was determined by in situ hybridisation. RESULTS: Six of 31 primary SS (19%) and one of 44 secondary SS (2%) serum samples were positive for anti-HCV by ELISA. Three samples were positive, three indeterminate, and one sample corresponding to a secondary SS patient was negative by immunoblot. The three immunoblot positive serum samples were also HCV-RNA positive by PCR assay. The study of lymphocytic cells in the diffuse infiltrate of minor salivary glands showed a predominance of the CD3 lymphocytic population. A predominance of CD4 over CD8 T cells (ratio 2:1) was observed in HCV and non-HCV infected patients. The analysis of the lymphocytic focus showed that the HCV infected patients had a predominance of CD20 positive cells. Activation molecules (CD-25 and HLA-DR) were expressed in HCV and non-HCV infected patients in lymphocytic and epithelial cells, however epithelial cell expression of CD25 was low in HCV infected patients. As expected, a pronounced Th1 response was observed in the lymphocytic foci of HCV patients. CONCLUSIONS: HCV infected patients may develop an autoimmune sialadenitis, similar to that described in primary SS.
10940907 Induction of experimental autoimmune arthritis by a public epitope of the T cell receptor 2000 Aug T cell receptor (TCR) peptide immunizations have been demonstrated to protect against experimental autoimmune diseases. These findings have led to clinical trials employing TCR peptides in multiple sclerosis and rheumatoid arthritis patients. Previously, we identified a strongly immunogenic region of the TCR alpha chain of an arthritogenic T cell clone (AV11 66-80). In this report, we show that rats immunized with AV11 66-80 developed arthritis with clinical symptoms and histology similar to adjuvant arthritis (AA). Transfer of this disease into naive rats using AV11 66-80-specific T cells proved the T cell-mediated character of the disease. The AV11 66-80 arthritic rats developed resistance to Mycobacterium tuberculosis-induced AA, indicating that both forms of arthritis depended on similar regulatory mechanisms. This first demonstration of TCR peptide-induced arthritis, together with an earlier report on a polymorphism in this very same AV11 66-80 region involved in arthritis resistance in mice, suggests a central role of the public epitope AV11 66-80 in the control of autoimmune arthritis. Although TCR peptide immunizations can be exploited to prevent experimental autoimmunity, caution should be taken in the induction of TCR peptide-specific T cells for immunotherapy to avoid adverse effects as shown here.
9324024 Association of a new allele of the TAP2 gene, TAP2*Bky2 (Val577), with susceptibility to S 1997 Sep OBJECTIVE: To investigate the polymorphisms of TAP (transporters associated with antigen processing) genes among patients with primary Sjögren's syndrome (SS) in order to clarify the potential association of the polymorphisms with disease susceptibility. METHODS: Polymorphisms of the TAP1 and TAP2 genes in 108 Japanese SS patients were determined by analyzing TAP genes using the polymerase chain reaction-single-stranded conformation polymorphism technique. RESULTS: The allelic frequency of the TAP1 gene was not significantly different between SS patients and normal subjects. In addition to all known TAP2 alleles, a new allele (Bky2), which had a unique substitution at codon 577 (ATG-->GTG: Met-->Val), was identified in both groups. The allelic frequency of Bky2 was significantly higher in SS patients (12.0%) than in normal subjects (5.1%) (P < 0.05). Moreover, a significantly greater frequency of SS-A antibody was found among SS patients with Bky2 (18 of 23; 78%) than among those without Bky2 (33 of 85; 39%) (P = 0.001). CONCLUSION: The mutation in TAP2 (Val577) may be involved in SS-A autoantibody production and could be a genetic factor that determines susceptibility to SS.
11525955 Cutaneous ulceration as a sign of methotrexate toxicity. 2001 Sep Methotrexate (MTX) inhibits DNA synthesis by competition with dihydrofolate reductase. Adverse cutaneous reactions to MTX are usually dose-related and have been mainly reported in patients receiving extremely large doses of chemotherapy. Painful erosion of psoriatic plaques has been often reported as an early sign of MTX toxicity, but cutaneous ulceration as a sign of MTX toxicity in patients without psoriasis has only been described in one case. We report a patient with rheumatoid arthritis and without psoriasis who developed cutaneous ulceration on the knuckles as a sign of MTX toxicity. Cutaneous ulceration by MTX toxicity is an exclusion diagnosis and its pathogenic mechanism may be multifactorial, including direct toxicity of the drug in addition to local factors.
11791633 Seroprevalence of Helicobacter pylori in primary Sjögren's syndrome. 2001 Nov OBJECTIVE: To study the seroprevalence of Helicobacter pylori (H. pylori) infection in patients with primary Sjögren's syndrome (SS), fulfilling the 1993 European classification criteria compared with three different control groups. METHODS: Serological tests investigating the presence of antibodies against H. pylori were performed by Enzyme Immuno Assay (EIA) and confirmed by immunoblot (IB). The samples were tested for antibodies against cytotoxin-associated-protein A (CagA). The three control groups included were: one simultaneously collected age-matched group of orthopaedic outpatients without rheumatological disease, a random primary care patient sample from the same geographic region and a group of age-matched blood donors. RESULTS: 45% of the SS patients (n = 164) were EIA-positive for H. pylori and 30% were positive in the confirming IB assay. 23% had antibodies to the CagA protein. We found a clear and statistically significant increase in seroprevalence with increasing age. These estimates were lower compared to the control group of orthopaedic patients but similar to those in the other two control groups, thus showing the importance of multiple control groups in case control studies. In the group of SS patients there were no significant associations between a positive EIA, IB or CagA for H. pylori and the presence of abnormal serum levels of autoantibodies (ANA, anti-SSA, anti-SSB, rheumatoid factor (RF)) or an abnormal lip biopsy. CONCLUSION: Swedish patients with primary SS do not have higher H. pylori seroprevalence rates than controls. Neither was H. pylori seropositivity associated with the presence of immunological markers of SS such as circulating autoantibodies or a lip biopsy with abnormal focus score.