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ID PMID Title PublicationDate abstract
14626802 Validity and reliability of the EQ-5D self-report questionnaire in Chinese-speaking patien 2003 Sep OBJECTIVE: We assessed the psychometric properties of a Singaporean Chinese version of the EQ-5D, a health-related quality of life (HRQoL) instrument. MATERIALS AND METHODS: Consecutive outpatients with rheumatic diseases seen for routine follow-up consultations at the National University Hospital, Singapore were interviewed twice within 2 weeks using a standardised questionnaire containing the EQ-5D, the Short-Form 36 Health Survey (SF-36), the Learned Helplessness Subscale, a pain Visual Analogue Scale (VAS) and assessing demographic and psychosocial characteristics. To assess the validity of the EQ-5D, 13 hypotheses relating the EQ-5D self-classifier (5 dimensions) or visual analogue scale (EQ-VAS) to SF-36 scores or other variables were examined using the Mann-Whitney U test, Kruskal-Wallis or Spearman's correlation coefficient. Test-retest reliability was assessed using Cohen's kappa. RESULTS: Forty-eight subjects were studied (osteoarthritis: 16; rheumatoid arthritis: 22; systemic lupus erythematosus: 8; spondyloarthropathy: 2; female: 93.8%; mean age: 56.4 years). Seven of 13 a-priori hypotheses relating EQ-5D to external variables were fulfilled, supporting the validity of the EQ-5D. For example, subjects reporting moderate or extreme problems for EQ-5D dimensions generally had lower median SF-36 scores than those without such problems. Cohen's kappa for test-retest reliability of the self-classifier ranged from 0.41 to 1.00 (n = 42; median interval: 7 days, interquartile range: 7 to 11 days). CONCLUSIONS: The Singaporean Chinese EQ-5D self-classifier appears to be a valid measure of HRQoL in Singaporeans with rheumatic diseases; however, the reliability of the EQ-VAS requires further investigation. These data provide a basis for further studies of the Singaporean Chinese EQ-5D.
14600656 Low fasting serum triglyceride level as a precocious marker of autoimmune disorders. 2003 Aug 7 The authors recently reported the occurrence of low fasting serum triglyceride (TG) and high free fatty acid (FFA) levels in idiopathic pulmonary fibrosis. TG estimation in diverse groups of patients with autoimmune disease or hyperactive immune response confirmed the occurrence of a similar decrease of TG. In some patients, serum FFA level was also evaluated. TG value in lean and obese patients was compared with that in lean (n = 108) and obese (n = 208) control subjects without autoimmune disease. In patients affected by autoimmune chronic thyroiditis with enhanced concentration of antithyroglobulin antibodies and without thyroidal failure (n = 24), lean and obese patients had reduced TG (-69/%, P < .01 and -52%, P < .0001, respectively). Both lean and obese patients affected by chronic active B or C hepatitis (n = 26), with autoantibodies and without signs of hepatic insufficiency or cirrhosis, presented reduced TG (-57%, P < .01 and -61%, P < .001, respectively). A marked TG decrease (-73%, P < .001) was observed in the lean patients affected by lupus-like syndrome (n = 7). The lean and obese patients with systemic lupus erythematosus or rheumatoid arthritis (n = 11) showed TG decrease (-66%, P < .01 and -55%, P < .05, respectively). In patients affected by anamnestic allergy or atopic dermatitis/asthma (n = 66), both lean and obese, TGs were reduced (-67%, P < .0001 and -62%, P < .001, respectively). In isolated cases of diverse autoimmune diseases (scleroderma, APECED [autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy], urticaria or urticarial vasculitis, Reiter or Sjogren syndromes, ulcerative colitis or Crohn's disease, multiple sclerosis or Guillain-Barré syndrome) (n = 14), decreased TG was also observed both in the lean and obese subjects (-59%, P < .01 and -57%, P < .01, respectively). Concerning FFA (n = 69), value in lean patients (n = 22) vs that in lean controls (n = 18) was increased (520 +/- 31 vs 299 +/- 30 mcEq/L, +74%, P < .001), whereas value in obese patients (n = 18) vs that in obese control subjects (n = 11) was decreased (542 +/- 34 vs 774 +/- 62, -30%, P < .01). This opposite behavior of FFA in lean and obese patients needs to be confirmed. Data in this study seem to indicate that low TG value may be a precocious marker of autoimmunity or immune system hyperreactivity.
12654381 Progressive outer retinal necrosis in immunocompetent patients treated initially for optic 2003 Apr PURPOSE: To report two cases of progressive outer retinal necrosis occurring in immunocompetent individuals after treatment with corticosteroids for presumed optic neuropathy. DESIGN: Observational case report. SETTING: University-based tertiary eye hospital. METHODS: Retrospective review of existing clinical records. RESULTS: Two patients were treated empirically with systemic corticosteroids for suspected inflammatory papillopathy. Subsequently, both were diagnosed with necrotizing herpetic retinitis with features of progressive outer retinal necrosis. Anterior chamber paracentesis confirmed varicella-zoster infection. Both patients were human immunodeficiency virus negative; one patient with rheumatoid arthritis was taking etanercept. Both became completely blind in one eye despite intensive treatment with antiviral medication intravenously and intravitreally. CONCLUSIONS: Progressive outer retinal necrosis is not confined to patients with underlying severe immunodeficiency, such as acquired immune deficiency syndrome. Initial treatment of acute, unexplained vision loss with systemic corticosteroids may lead to catastrophic visual loss in patients with evolving necrotizing herpetic retinopathy.
12563366 [Detection of serum anti-B/B' UsnRNP antibodies in patients with connective tissue disease 2002 Oct OBJECTIVE: To investigate the reliability of the immunoblot method in the detection of serum immunoreactivity towards the B/B' polypeptides of U small nuclear ribonucleoproteins (UsnRNP) and to assess the significance of these antibodies in connective tissue disease (CTD) patients. METHODS: We tested the sera of 348 patients with CTD (101 SLE, 51 systemic sclerosis, 53 primary Sjögren's syndrome, 27 poly/dermatomyositis, 15 rheumatoid arthritis and 101 overlap CTD), of 31 matched healthy subjects and 13 patients with primary Epstein-Barr virus (EBV) infection with high titre of IgG anti-EBV antibodies. IgG anti-UsnRNP antibodies were determined by immunoblotting on nuclear extract from Raji cells (an EBV-immortalised human B lymphoid cell line) and Jurkat cells (a human T lymphoid cell line). Anti-dsDNA antibodies were detected by indirect immunofluorescence on Crithidia luciliae and anti-ENA by counterimmunoelectrophoresis. Anti-dsDNA activity and avidity were measured in SLE sera by ELISA with Scatchard analysis. Results were statistically analysed by chi-square and Mann-Whitney tests. RESULTS: A high frequency of anti-B/B' antibodies was found in the sera of CTD patients, confined to SLE (54.4%) and overlap CTD with SLE features (55,2%). Anti-B/B' immune reactivity was closely associated with other anti-UsnRNP specificities, gel precipitating anti-nRNP and anti-P antibodies. Nine out of 15 (60%) anti-B/B' positive/anti-ENA negative lupus sera on Raji blots were confirmed to be positive also on Jurkat blots. The sera from patients with EBV infection provided, on Raji blots, completely different band patterns from those obtained with auto-immune sera. CONCLUSIONS. The Sm B/B' proteins are the predominant or, at least, the most frequently targeted antigens of the UsnRNP auto-immune response in SLE and "lupus-like" overlap CTD. Moreover, anti-B/B' is diagnostically specific for CTD with SLE features. Immunoblotting on human B lymphoid cells is a reliable method, in terms of sensitivity and specificity, for the detection of anti-Sm B/B' antibodies.
12508119 Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. 2003 Jan 23 Excessive inflammation and tumour-necrosis factor (TNF) synthesis cause morbidity and mortality in diverse human diseases including endotoxaemia, sepsis, rheumatoid arthritis and inflammatory bowel disease. Highly conserved, endogenous mechanisms normally regulate the magnitude of innate immune responses and prevent excessive inflammation. The nervous system, through the vagus nerve, can inhibit significantly and rapidly the release of macrophage TNF, and attenuate systemic inflammatory responses. This physiological mechanism, termed the 'cholinergic anti-inflammatory pathway' has major implications in immunology and in therapeutics; however, the identity of the essential macrophage acetylcholine-mediated (cholinergic) receptor that responds to vagus nerve signals was previously unknown. Here we report that the nicotinic acetylcholine receptor alpha7 subunit is required for acetylcholine inhibition of macrophage TNF release. Electrical stimulation of the vagus nerve inhibits TNF synthesis in wild-type mice, but fails to inhibit TNF synthesis in alpha7-deficient mice. Thus, the nicotinic acetylcholine receptor alpha7 subunit is essential for inhibiting cytokine synthesis by the cholinergic anti-inflammatory pathway.
12459173 Autoantibody to DNA binding protein B as a novel serologic marker in systemic sclerosis. 2002 Dec 13 Systemic sclerosis is a systemic disease that is characterized by tissue fibrosis, small-vessel vasculopathy, and an autoimmune response associated with autoantibodies. We performed serological analysis of cDNA expression library (SEREX) to identify autoantibodies associated with systemic sclerosis. We identified 4 clones that react with sera of patients with SSc but not with those of healthy donors. These clones are phosphoglycerate mutase, centromere autoantigen C, U1 small nuclear ribonucleoprotein, and DNA binding protein B (dbpB). We chose to study autoantibody to DNA binding protein B. Immunoreactivity against recombinant dbpB was detected in 40.5% (15/37) of patients with SSc, 14.6% (6/41) of patents with systemic lupus erythematosus, 6.7% (1/15) of patients with rheumatoid arthritis, 0% (0/12) of patients with Sjogren syndrome, and 5.9% (1/17) of patients with polymyositis/dermatomyositis. The frequency of anti-dbpB was significantly higher in the SSc patients (15/37, 40.5%) compared to the healthy controls (3/41, 7.3%, p=0.0005 by chi(2) test). Eleven patients (11/20, 55%) with the diffuse cutaneous type of SSc had anti-dbpB and 4 patients (4/17, 23.5%) with the limited cutaneous type had anti-dbpB. The presence of anti-dbpB was significantly associated with the diffuse cutaneous type (p=0.00003 by chi(2) test). This is the first report to suggest that autoantibody to dbpB can be used as a serologic marker of systemic sclerosis.
12379362 Catalytic antibodies in clinical and experimental pathology: human and mouse models. 2002 Nov 1 Most of the data accumulated through studies on natural catalytic autoantibodies indicate that production scales up markedly in pathological abnormalities. We have previously described an increased level of DNA-hydrolyzing autoantibodies in the sera of patients with various autoimmune disorders [systemic lupus erythematosus (SLE), rheumatoid arthritis, scleroderma], HIV infection and lymphoproliferative diseases accompanied by autoimmune manifestations. In the present study, we show that an increased level of catalytic activity of autoantibodies can be observed in the sera of autoimmune mice, thus providing a fundamental insight into the medical relevance of abzymes. Polyclonal autoantibodies purified from sera of NZB/W, MRL-lpr/lpr and SJL/J mice show proteolytic and DNA-hydrolyzing activities, as opposed to those harvested from non-autoimmune BALB/c mice. The expressiveness of the catalytic activity was strongly dependent on the age of the animal. The highest levels of catalytic activity were found in the sera of mice aged between 8 and 12 months; the lowest level was typical of younger animals whose age ranged from 6 to 8 weeks. Specific inhibition assays of the catalytic activities were performed to throw light on the nature of the abzyme activity. Within a cohort of aging animals, a strong correlation between marked autoimmune abnormalities and levels of catalytic activities has been established. Nonimmunized SJL/J mice revealed specific immune responses to myelin basic protein (MBP), skeletal muscle myosin (skMyo) and cardiac myosin (Myo), and highly purified antibodies from their serum show specific proteolytic attack against the target antigens. This finding prompted us to undertake a more detailed study of specific antibody-mediated proteolysis in diseased humans. A targeted catalytic response was originally demonstrated against MBP and Myo in multiple sclerosis and myocarditis patients, respectively.
12220104 Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with systemic lup 2002 Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease that may affect every organ or system in the body. We have shown previously that the TCR alphabeta+ subpopulation of CD3+ CD4- CD8-, DN T cells is expanded in patients with SLE and that double negative T cells express increased levels of activation markers compared both with healthy people and with patients with rheumatoid arthritis, (RA) as autoimmune controls. The aim of this study was to characterize these cells in terms of their ability to produce IL4, a Th2 cytokine, both spontaneously and after mitogen stimulation. It was found that a higher percentage of TCR alphabeta+ double negative T cells from patients with SLE contained IL4 constitutively than did the same population of cells from healthy people or from those with RA. After mitogen stimulation, there was no significant difference in the amount of IL4 produced by each of the three groups. Further study of patients producing high levels of IL4 (about one third of the patients) indicated that they had a lower percentage of alphabeta+ T cells in the double negative compartment than did patients with fewer IL4 containing cells.
12218161 Restriction of de novo pyrimidine biosynthesis inhibits Th1 cell activation and promotes T 2002 Sep 15 Leflunomide, an inhibitor of de novo pyrimidine biosynthesis, has recently been introduced as a treatment for rheumatoid arthritis in an attempt to ameliorate inflammation by inhibiting lymphocyte activation. Although the immunosuppressive ability of leflunomide has been well described in several experimental animal models, the precise effects of a limited pyrimidine supply on T cell differentiation and effector functions have not been elucidated. We investigated the impact of restricted pyrimidine biosynthesis on the activation and differentiation of CD4 T cells in vivo and in vitro. Decreased activation of memory CD4 T cells in the presence of leflunomide resulted in impaired generation and outgrowth of Th1 effectors without an alteration of Th2 cell activation. Moreover, priming of naive T cells in the presence of leflunomide promoted Th2 differentiation from uncommitted precursors in vitro and enhanced Th2 effector functions in vivo, as indicated by an increase in Ag-specific Th2 cells and in the Th2-dependent Ag-specific Ig responses (IgG1) in immunized mice. The effects of leflunomide on T cell proliferation and differentiation could be antagonized by exogenous UTP, suggesting that they were related to a profound inhibition of de novo pyrimidine biosynthesis. These results indicate that leflunomide might exert its anti-inflammatory activities in the treatment of autoimmune diseases by preventing the generation of proinflammatory Th1 effectors and promoting Th2 cell differentiation. Moreover, the results further suggest that differentiation of CD4 T cells can be regulated at the level of nucleotide biosynthesis.
12203906 A new concept: the use of vanadium complexes in the treatment of diabetes mellitus. 2002 In the 21st century, patients suffering from diabetes mellitus (DM), a lifestyle-related disease, will increase more than in the 20th century. DM is threatening because of the development of many severe secondary complications, including atherosclerosis, microangiopathy, renal dysfunction and failure, cardiac abnormalities, diabetic retinopathy, and ocular disorders. Generally, DM is classified as either insulin-dependent type 1 or noninsulin-dependent type 2 DM. Type 1 DM is treated only by daily insulin injections; type 2 DM is treated by several types of synthetic therapeutic substances together with a controlled diet and physical exercise. Even with these measures, the daily necessity for several insulin injections can be painful both physically and mentally, whereas the synthetic therapeutic substances used over the long term often have side effects. For those reasons, the creation and development of a new class of pharmaceuticals for treatment of DM in the 21st century would be extremely desirable. In the last half of the 20th century, investigations of the relationships among diseases and micronutrients, such as iron, copper, zinc, and selenium, have been numerous. Research into the development of metallopharmaceuticals involving the platinum-containing anticancer drug, cisplatin, and the gold-containing rheumatoid arthritis drug, auranofin, has also been widespread. Such important findings prompted us to develop therapeutic reagents based on a new concept to replace either insulin injections or the use of synthetic drugs. After many trials, we noticed that vanadium might be very useful in the treatment of DM. Before the discovery of insulin by Banting and Best in 1921 and its clinical trial for treating DM, the findings in 1899, in which orally administered sodium vanadate (NaVO(3)) was reported to improve human DM, gave us the idea to use vanadium to treat DM. However, it has taken a long time to obtain a scientific explanation as to why the metal ion exhibits insulin-mimetic or blood-glucose lowering effects in in vitro and in vivo experiments. After investigations from many perspectives involving biochemistry and bioinorganic chemistry, vanadyl sulfate (VOSO(4)) and its complexes with several types of ligands have been proposed as useful for treating DM in experimental diabetic animals. On the basis of a mechanistic study, this article reports on recent progress regarding the development of antidiabetic vanadyl complexes, emphasizing that the vanadyl ion and its complexes are effective not only in treating or relieving both types of DM but also in preventing the onset of DM.
12137622 Dietary marine fatty acids (fish oil) for asthma in adults and children. 2002 BACKGROUND: Epidemiological studies suggest that a diet high in marine fatty acids (fish oil) may have beneficial effects on inflammatory conditions such as rheumatoid arthritis and possibly asthma. OBJECTIVES: 1. To determine the effect of marine n-3 fatty acid (fish oil) supplementation in asthma. 2. To determine the effect of a diet high in fish oil in asthma. SEARCH STRATEGY: The Cochrane Airways Review Group register was searched using the terms: marine fatty acids OR diet OR nutrition OR fish oil OR eicosapentaenoic acid OR EPA. Bibliographies of retrieved trials were searched and fish oil manufacturers contacted. SELECTION CRITERIA: Randomised controlled trials in patients with asthma more than two years of age were included. The study duration had to be in excess of four weeks. Double blind trials were preferred, but single-blind and open trials were also reviewed for possible inclusion. Three reviewers read each paper, blind to its identity. Decisions concerning inclusion were made by simple majority. Quality assessment was performed by all three reviewers independently. DATA COLLECTION AND ANALYSIS: The only comparison possible was between marine n-3 fatty acid supplementation and placebo. There were insufficient trials to examine dietary manipulation alone. MAIN RESULTS: Nine randomised controlled trials conducted between 1986 and 2001 satisfied the inclusion criteria. Seven were of parallel design and two were cross-over studies. Eight compared fish oil with placebo whilst one compared high dose vs low dose marine n-3 fatty acid supplementation. Two studies were conducted in children, whilst the remaining seven studies were conducted in adults. None of the included studies reported asthma exacerbations, health status or hospital admissions. There was no consistent effect on any of the analysable outcomes: FEV1, peak flow rate, asthma symptoms, asthma medication use or bronchial hyper reactivity. One of the studies performed in children which combined dietary manipulation with fish oil supplementation showed improved peak flow and reduced asthma medication use. There were no adverse events associated with fish oil supplements. REVIEWER'S CONCLUSIONS: There is little evidence to recommend that people with asthma supplement or modify their dietary intake of marine n-3 fatty acids (fish oil) in order to improve their asthma control. Equally, there is no evidence that they are at risk if they do so.
11853703 Effects of a selective cyclooxygenase-2 inhibitor, celecoxib, on bone resorption and osteo 2002 Feb 1 The effects of an important new anti-inflammatory agent, the selective cyclooxygenase-2 inhibitor celecoxib, on bone resorption and osteoclastogenesis elicited by the inflammatory cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha), the endotoxin lipopolysaccharide (LPS), and the systemic hormones 1alpha,25-dihydroxyvitamin D(3) and parathyroid hormone were examined in vitro. Bone resorption was evaluated by measuring calcium released into the culture medium in a neonatal mouse calvarial bone organ culture. Osteoclastogenesis was evaluated by measuring tartrate-resistant acid phosphatase activity in the cells in cocultures of bone marrow cells and osteoblastic cells and in macrophage-colony-stimulating factor-dependent bone marrow cell cultures. Celecoxib (0.1 microM) completely inhibited the calcium release induced by IL-1beta, TNF-alpha, and LPS. The resorptive effect of 1alpha,25-dihydroxyvitamin D(3) was inhibited partially by celecoxib. In contrast, celecoxib did not inhibit the calcium release elicited by parathyroid hormone or prostaglandin E(2). Celecoxib (0.1 microM) also markedly inhibited osteoclastogenesis induced by these stimulators of bone resorption except for PGE(2) in the coculture system, whereas it failed to inhibit osteoclastogenesis in macrophage-colony-stimulating factor-dependent bone marrow cell cultures. These results indicate that, under certain conditions, cyclooxygenase-2-dependent prostaglandin synthesis is critical for the bone resorption induced by IL-1beta, TNF-alpha, and LPS, and for the osteoclastogenesis induced by these pro-inflammatory molecules and calciotropic hormones. The prevention of prostaglandin synthesis by inflammatory cytokines in bone cells could contribute to the efficacy of celecoxib in preventing bone loss in rheumatoid arthritis.
20641472 (111)In-Tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-Glu-cyclo(Arg-Gly-Asp-D-Phe-L 2004 Integrins are a family of heterodimeric glycoproteins on cell surfaces that mediate diverse biological events involving cell–cell and cell–matrix interactions (1). Integrins consist of an α and a β subunit and are important for cell adhesion and signal transduction. The α(v)β(3) integrin is the most prominent receptor affecting tumor growth, tumor invasiveness, metastasis, tumor-induced angiogenesis, inflammation, osteoporosis, and rheumatoid arthritis (2-7). Expression of the α(v)β(3) integrin is strong on tumor cells and activated endothelial cells, whereas expression is weak on resting endothelial cells and most normal tissues. Antagonists of α(v)β(3) are being studied as antitumor and antiangiogenic agents, and the agonists of α(v)β(3) are being studied as angiogenic agents for coronary angiogenesis (6, 8, 9). A tripeptide sequence consisting of Arg-Gly-Asp (RGD) has been identified as a recognition motif used by extracellular matrix proteins (vitronectin, fibrinogen, laminin, and collagen) to bind to a variety of integrins, including α(v)β(3). Various radiolabeled antagonists have been introduced for imaging of tumors and tumor angiogenesis (10). Most cyclic RGD peptides are composed of five amino acids. Haubner et al. (11) reported that various cyclic RGD peptides exhibit selective inhibition of binding to α(v)β(3) (inhibition concentration (IC(50)), 7–40 nM) but not to integrins α(v)β(5) (IC(50), 600–4,000 nM) or α(IIb)β(3) (IC(50), 700–5,000 nM). Various radiolabeled cyclic RGD peptides have been found to have high accumulation in tumors in nude mice (12). Dijkgraaf et al. (13) reported the development of (111)In-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid-Glu-cyclo(Arg-Gly-Asp-D-Phe-Lys) ((111)In-DOTA-E-c(RGDfK)) for imaging α(v)β(3) receptors in nude mice bearing ovarian carcinoma tumors.
11991968 Regulation of tumor necrosis factor alpha promoter by human parvovirus B19 NS1 through act 2002 Jun Human parvovirus B19 frequently causes acute and chronic arthritis in adults. The molecular mechanism of B19 arthritis, however, remains poorly understood. We previously showed that the transmission of B19 from rheumatoid synoviocytes to monocytic cells is associated with enhanced secretion of tumor necrosis factor alpha (TNF-alpha), which triggers inflammation, and interleukin-6. To determine the role of B19 in the production of TNF-alpha, we focused on the function of its nonstructural protein, NS1, and established monocytic U937 lines transduced with the NS1 gene under the control of an inducible promoter. Production of TNF-alpha mRNA and protein was elevated in a manner associated with NS1 expression. Reporter assays revealed that AP-1 and AP-2 motifs on the TNF-alpha promoter were responsible for NS1-mediated up-regulation. Electrophoretic mobility shift assay showed specific binding of nuclear proteins from NS1 gene-transduced cells with the AP-1 or AP-2 probe. Antibodies against transcription factors AP-1 and AP-2 and anti-NS1 antibody inhibited the binding of nuclear proteins to the corresponding probes. These data indicate that NS1 up-regulates TNF-alpha transcription via activation of AP-1 and AP-2 in monocytic cells. The molecular mechanisms of NS1-mediated TNF-alpha expression would explain the pathogenesis of B19-associated inflammation.
12067313 The Th1/Th2 cytokine balance changes with the progress of the immunopathological lesion of 2002 Jun Expression of type-1 and type-2 cytokines at the mRNA level in labial salivary glands (LSG) of patients with Sjogren's syndrome (SS), as reported by several groups, have generated conflicting results. In the present study we have directly examined the production of IL-4, IL-13 and IFN-gamma by lymphocytes infiltrating the LSG of 44 consecutive patients referred for SS evaluation. Cytokines production was evaluated following in vitro culture of LSG in the presence of IL-2. IFN-gamma and IL-13 were detected in the majority of SN (24/44 and 26/44, respectively) while IL-4 was present in 5/44 SN. The presence of IFN-gamma was significantly higher in SS patients, as opposed to patients who did not fulfil the criteria for SS (P < 0.01). In addition, almost all cultured lymphocytes expressed mRNA for IFN-gamma (17/19 cultures) and IL-13 (18/19) while IL-4 mRNA was also expressed at high frequency (14/19 cultures). Interestingly, the IFN-gamma mRNA copies in cultured lymphocytes correlated significantly with the intensity of lymphocytic infiltration as evaluated by Chisholm's score (P < 0.01). Furthermore, RT-PCR of RNA extracted from whole LSG from 14 SS patients also demonstrated the presence of all cytokines in the majority of the cases and the prevalence of IFN-gamma in LSG with high-grade infiltration. Because IL-13 was produced by the majority of the cultured LSG, IgE production was also evaluated. Interestingly, IgE was detected in 21/44 LSG culture SN and mainly in those biopsies that had Chisholm's score less than 0.5 (P < 0.05). We conclude that lymphocytes infiltrating the LSG are capable of producing both Th1 and Th2 cytokines and that the balance between them shifts in favour of Th1 in LSG with high infiltration score and in patients with SS.
15448705 Inhibitory effects of autoantibodies on the muscarinic receptors in Sjögren's syndrome. 2004 Nov Sjogren's syndrome (SS) is a systemic autoimmune disease that involves reduced salivary secretions. Recently, circulating autoantibodies from SS patients against the type 3 muscarinic cholinergic receptor (M3R) has been reported in the sera of SS patients. However, the role of these autoantibodies in the development of SS has not been elucidated. In this study, purified IgG was obtained from the sera of 11 SS patients, and its inhibitory effect on the M3R of the salivary glands was evaluated using RT-PCR, microspectrofluorimetry, immunohistochemistry, and Western blot analysis. Stimulation with carbachol (CCh) evoked a [Ca2+]i transient in the fura-2 loaded HSG cells. However, pretreatment of the cells with SS IgG (0.5 mg/ml) for 12 or 24 h significantly reduced the magnitude of the CCh-induced [Ca2+]i transient (CICT). We found that the magnitude of CICT was decreased by 62-45% when cells were pretreated with the SS IgG. However, the [Ca2+]i response to ATP was not altered by the pretreatment of SS IgG. The effect of SS IgG on CICT was abrogated by the inclusion of excessive competitive peptides that encode the amino-acid sequence of M3R, which was not recapitulated by nonspecific peptides. The inhibitory effect of SS IgG on the aquaporin (AQP)-5 expression was also examined. After confirming the apical localization of AQP-5 along with its increase by pilocarpine (10(-5) M), we examined whether SS IgG had an effect on pilocarpine-induced AQP-5 trafficking to the apical membrane (APM) using rat parotid acinar cells. After incubating the cells with SS IgG for 12 h, the amount of pilocarpine-induced AQP-5 significantly decreased compared to the control groups. In conclusion, autoantibodies from the SS patients inhibit the function of the human M3R that is mediated by Ca2+ mobilization and AQP-5 trafficking. Our results could partly explain the underlying mechanisms of glandular dysfunction and associated features of impaired autonomic function in SS patients.
12955689 Primary Sjögren's syndrome associated with Gitelman's syndrome presenting with muscular p 2003 Sep A 38-year-old woman presented with muscle cramping of 4 extremities and paralysis for months. Laboratory results showed an elevated antinuclear antibody titer; antibodies to the ribonucleoprotein antigen Ro; hypokalemia; hypomagnesemia with hyperreninemia, but abnormally high urine potassium and magnesium levels and low urine calcium levels; and a blunted diuretic effect to thiazide, but not furosemide, which met the criteria for Gitelman's syndrome (GS) and led to the diagnosis of primary Sjögren's syndrome (pSS). She received medical treatment, including a potassium supplement and aldosterone antagonist. GS as a presentation of pSS has never been reported in the literature. The features of renal diseases related to SS are reviewed. SS is the underlying cause of GS, which may precede the onset of the well-known sicca complex.
12783421 The spectrum of autoimmune autonomic neuropathies. 2003 Jun We analyzed the clinical characteristics of 18 patients (13 female, 5 male) who had autoimmune autonomic neuropathy (AAN) and ganglionic acetylcholine receptor (AChR) autoantibodies. Mean age was 61.4 years (standard deviation, 12.0 years). Ten patients had subacute symptom onset, six with an antecedent event. Eight patients had chronic AAN, characterized by insidious symptom onset, without antecedent event, and gradual progression. A majority of patients with high antibody values (>1.00 nmol/L) had a combination of sicca complex (marked dry eyes and dry mouth), abnormal pupillary light response, upper gastrointestinal symptoms, and neurogenic bladder. Chronic AAN segregated into two subgroups. One subgroup (N = 4) had low antibody titer (0.09 +/- 0.01 nmol/L) and a paucity of cholinergic symptoms. It was indistinguishable from pure autonomic failure. The other subgroup (N = 4) had high antibody titer (11.6 +/- 2.08 nmol/L), sicca complex, abnormal pupils, and neurogenic bladder; three had severe upper gastrointestinal dysfunction. Higher antibody titers correlated with greater autonomic dysfunction and more frequent cholinergic dysautonomia. These observations expand the clinical spectrum of AAN to include chronic cases, some being indistinguishable from pure autonomic failure, and support the concept that ganglionic AChR antibodies are important diagnostically and pathophysiologically in acquired dysautonomia.
15149517 Autoimmune thyroid disease in anti-Ro/SS-A-positive children with annular erythema: report 2004 May Anti-Ro/SS-A-associated recurrent annular erythema is a rare disorder, and represents a cutaneous manifestation of primary Sjögren's syndrome (SS). We report two childhood cases complicated with autoimmune thyroid disease, one with Graves' disease and the other with autoimmune thyroiditis. Both children were positive for anti-Ro/SS-A and anti-La/SS-B antibodies. One patient was lacking clinical SS with objective evidence of salivary gland involvement, while the other was diagnosed with primary SS. Our observation suggests that autoimmune thyroid disease in the subset of anti-Ro/SS-A-positive children with annular erythema might occur with similar frequency to that in adult primary SS.
12360791 [Antibodies against recombinant Ro 60 Kd, Ro 52 and La 48 Kd proteins in primary Sjogren's 2002 Aug BACKGROUND: The use of new recombinant antigens may increase the sensitivity and specificity of the detection of anti Ro and anti La antibodies in Sjögren's syndrome. AIM: To determine the immune reactivity of sera from patients with Sjögren's syndrome, against fusion recombinant proteins (prf) Ro60 Kd, Ro52 Kd and La48 Kd expressed in E coli and recombinant protein Ro52 Kd, expressed in baculovirus (prb). MATERIAL AND METHODS: Serum samples from 46 patients with a diagnosis of Sjögren's syndrome, according to the European criteria of 1997, were studied. Using conventional ELISA assays, 32 patients had positive anti Ro antibodies (group A) and 16 patients had negative anti Ro and anti La antibodies, but had positive antinuclear antibodies or rheumatoid factors (group B). Antibodies against recombinant proteins were measured by ELISA or Western Blot. RESULTS: Reactivity against prf Ro60 was present in 69% of samples from group A patients and in 36% of samples from group B. Reactivity against prf Ro52 was present in 94% of samples from group A and 50% of samples from group B. Reactivity against prb Ro52 was present in 75% of samples from group A and 40% of samples from group B. Reactivity against prf La was present in 78% of samples by ELISA and 97% of samples by Western Blot. In 10 of 14 serum samples from group B patients, there was reactivity against at least one recombinant protein. CONCLUSIONS: A high prevalence of reactivity against recombinant Ro and La proteins was detected in serum samples from patients with Sjögren syndrome.