Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
19531755 Is screening for hepatitis B and hepatitis C useful in patients with recent-onset polyarth 2009 Jul OBJECTIVE: To evaluate the seroprevalence of hepatitis B (HBV) and C (HCV) in patients living in France with recent-onset polyarthritis suggesting rheumatoid arthritis. METHODS: The 813 patients in the ESPOIR cohort were screened for anti-HCV antibodies and HBs antigen. RESULTS: Seroprevalence was 0.86% for HCV (n = 7) and 0.12% for HBV (n = 1). HCV-related arthritis was diagnosed in 4 (0.5%) patients; no patient had HBV-related arthritis. HCV-seropositive patients had significantly higher transaminase levels (ALAT, 41.5 IU vs 23.2 IU, p = 0.02; and ASAT, 39.2 IU vs 21.8 IU, p = 0.001) but only 2 patients had ASAT or ALAT levels > 40 IU. No significant differences were found for anti-CCP antibodies, C-reactive protein, erythrocyte sedimentation rate, or other test. HCV seroprevalence was significantly higher in the subgroup with history of blood transfusion than in other patients (3.7% vs 0.42%, p = 0.02). Two of the 7 HCV positive patients and the single patient with confirmed hepatitis B infection were born in areas with higher prevalence of viral hepatitis (Togo, Senegal, Vietnam). Positive hepatitis status was known before study inclusion in 4 of the 7 HCV-positive patients and in the HBV-positive patient. CONCLUSION: The prevalence of HBV and HCV in a population of patients with recent-onset polyarthritis suggestive of RA was not greater than expected based on data from the general population in the same geographic area. Routine HBV and HCV serological testing did not contribute substantially to the diagnosis of recent-onset polyarthritis. Although advisable before initiating immunosuppressive or hepatotoxic drugs, serological testing for HCV and HBV is unnecessary in routine diagnostic evaluation of recent-onset polyarthritis.
20682070 Visualization and phenotyping of proinflammatory antigen-specific T cells during collagen- 2010 INTRODUCTION: The Vβ12-transgenic mouse was previously generated to investigate the role of antigen-specific T cells in collagen-induced arthritis (CIA), an animal model for rheumatoid arthritis. This mouse expresses a transgenic collagen type II (CII)-specific T-cell receptor (TCR) β-chain and consequently displays an increased immunity to CII and increased susceptibility to CIA. However, while the transgenic Vβ12 chain recombines with endogenous α-chains, the frequency and distribution of CII-specific T cells in the Vβ12-transgenic mouse has not been determined. The aim of the present report was to establish a system enabling identification of CII-specific T cells in the Vβ12-transgenic mouse in order to determine to what extent the transgenic expression of the CII-specific β-chain would skew the response towards the immunodominant galactosylated T-cell epitope and to use this system to monitor these cells throughout development of CIA. METHODS: We have generated and thoroughly characterized a clonotypic antibody, which recognizes a TCR specific for the galactosylated CII(260-270) peptide in the Vβ12-transgenic mouse. Hereby, CII-specific T cells could be quantified and followed throughout development of CIA, and their phenotype was determined by combinatorial analysis with the early activation marker CD154 (CD40L) and production of cytokines. RESULTS: The Vβ12-transgenic mouse expresses several related but distinct T-cell clones specific for the galactosylated CII peptide. The clonotypic antibody could specifically recognize the majority (80%) of these. Clonotypic T cells occurred at low levels in the naïve mouse, but rapidly expanded to around 4% of the CD4+ T cells, whereupon the frequency declined with developing disease. Analysis of the cytokine profile revealed an early Th1-biased response in the draining lymph nodes that would shift to also include Th17 around the onset of arthritis. Data showed that Th1 and Th17 constitute a minority among the CII-specific population, however, indicating that additional subpopulations of antigen-specific T cells regulate the development of CIA. CONCLUSIONS: The established system enables the detection and detailed phenotyping of T cells specific for the galactosylated CII peptide and constitutes a powerful tool for analysis of the importance of these cells and their effector functions throughout the different phases of arthritis.
20480357 Arthroscopic debridement and biological resurfacing of the glenoid in glenohumeral arthrit 2010 Dec The purpose of this study was to analyse the intermediate-term results of an arthroscopic procedure to debride and resurface the arthritic glenoid, in a middle-aged population, using an acellular human dermal scaffold. Between 2003 and 2005, thirty-two consecutive patients underwent an arthroscopic debridement and biological glenoid resurfacing for glenohumeral arthritis. The diagnoses included primary osteoarthrosis (28 patients), arthritis after arthroscopic reconstruction for anterior instability (1 patient) and inflammatory arthritis (3 patients). All shoulders were assessed clinically using the Constant and Murley score, and results graded according to Neer's criteria. Statistical analysis was performed to determine significant parameters and associations. A significant improvement (P < 0.0001) in each parameter of the subjective evaluation component (severity of pain, limitation in daily living and recreational activities) of the Constant score was observed. The Constant and Murley score increased significantly (P < 0.0001) from a median of 40 points (range 26-63) pre-operatively to 64.5 (range 19-84) at the final assessment. Overall, the procedure was considered as "successful outcome" in 23 patients (72%) and as a "failure" in 9 patients (28%). According to Neer's criteria, the result was categorized as excellent in 9 (28%), satisfactory in 14 (44%) and unsatisfactory in 9 (28%). Within the unsatisfactory group, there were five conversions to prosthetic arthroplasty. A standard magnetic resonance imaging was performed on 22 patients in the successful outcome group; glenoid cartilage was identified in 12 (thick in 5, intermediate in 1, thin in 6) and could not be identified in 10 patients (complete/incomplete loss in 5, technical difficulties in 5). Overall, five complications included transient axillary nerve paresis, foreign-body reaction to biological material, inter-layer dissociation, mild chronic non-specific synovitis and post-traumatic contusion. Dominance of affected extremity and generalized disease (diabetes, rheumatoid arthritis, generalized osteoarthritis) was associated with an unsatisfactory outcome (P < 0.05). Arthroscopic debridement and biological resurfacing of the glenoid is a minimally invasive therapeutic option for pain relief, functional improvement and patient satisfaction, in glenohumeral osteoarthritis, in the intermediate-term.
19098927 The role of ADAMTS-7 and ADAMTS-12 in the pathogenesis of arthritis. 2009 Jan Loss of articular cartilage caused by extracellular matrix breakdown is the hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix protein (COMP) have been observed in arthritic patients. ADAMTS-7 and ADAMTS-12, two members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family, have been associated with COMP degradation in vitro, and are significantly overexpressed in the cartilage and synovium of patients with rheumatoid arthritis. Recent studies have demonstrated the importance of COMP degradation by ADAMTS-7 and ADAMTS-12. Specifically, the size of COMP fragments generated by ADAMTS-7 or ADAMTS-12 is similar to that of COMP-degradative fragments seen in arthritic patients. In addition, antibodies against ADAMTS-7 or ADAMTS-12 dramatically inhibit tumor necrosis factor-induced and interleukin-1beta-induced COMP degradation in cartilage explants. Furthermore, suppression of ADAMTS-7 or ADAMTS-12 expression using the small interfering RNA silencing approach in human chondrocytes markedly prevents COMP degradation. COMP degradation mediated by ADAMTS-7 and ADAMTS-12 is inhibited by alpha(2)-macroglobulin. More significantly, granulin-epithelin precursor, a newly characterized chondrogenic growth factor, disturbs the interaction between COMP and ADAMTS-7 and ADAMTS-12, preventing COMP degradation by these enzymes. This Review summarizes the evidence demonstrating that ADAMTS-7 and ADAMTS-12 are newly identified enzymes responsible for COMP degradation in arthritis, and that alpha(2)-macroglobulin and granulin-epithelin precursor represent their endogenous inhibitors.
21808547 Antiarthritic and antioxidant effects of the leaf extract of Ficus exasperata P. Beauv. (M 2010 Mar Leaf extracts of Ficus exasperata P. Beauv. (Moraceae) are commonly used in Ghanaian traditional medicine for the treatment of several pathological states including inflammatory disorders. The present study was undertaken to evaluate the antiarthritic effect of an ethanolic extract of F. exasperata (FEE) in the Freund's adjuvant-induced arthritis model in rats. Since free radicals and reactive oxygen species are implicated in inflammatory joint diseases such as rheumatoid arthritis, the antioxidant potential of the extract was investigated in in vitro experimental models. FEE as well as the positive controls, dexamethasone and methotrexate, showed significant dose-dependent antiarthritic properties when applied to established adjuvant arthritis. Oral administration of FEE (30-300 mg/kg p.o.) significantly reduced the arthritic edema in the ipsilateral paw of rats with a maximal inhibition of 34.46 ± 11.42%. FEE (30-300 mg/kg p.o.) also significantly prevented the spread of the edema from the ipsilateral to the contralateral paws indicating inhibition of systemic spread. The disease-modifying antirheumatic drug methotrexate (0.1-1 mg/kg i.p.) and the steroidal anti-inflammatory agent dexamethasone (0.3-3 mg/kg i.p.) also reduced very significantly the total polyarthritic edema as well as the spread of the arthritis from the ipsilateral to the contralateral paws of the treated animals. The extract also exhibited reducing activity (EC(50) = 8.105 ± 18.49), scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH, EC(50) = 0.499 ± 0.302) and prevented lipid peroxidation (IC(50) = 1.283 ± 0.923) in rat brain homogenates. Phenols were detected in the extract. These results suggest that ethanolic extract of the leaves of F. exasperata exerts antiarthritic activity after oral administration and also has antioxidant properties which may contribute to its activity.
20807027 Gut colonization by Candida albicans aggravates inflammation in the gut and extra-gut tiss 2011 Apr We examined whether Candida albicans gut colonization aggravates immune diseases in mice. Chronic and latent C. albicans gut colonization was established by the intragastric inoculation of C. albicans in mice fed as part of a purified diet. Allergic diarrhea was induced by repetitive intragastric administration of ovalbumin in sensitized BALB/c mice. Contact hypersensitivity was evaluated by measuring ear swelling after topical application of 2, 4-dinitrofluorobenzene in NC/Nga mice. Arthritis was induced by intradermal injection of bovine type-II collagen emulsified with complete Freund's adjuvant in DBA/1J mice. C. albicans gut colonization increased the incidence of allergic diarrhea, which was accompanied by gut hyperpermeability, as well as increased infiltration of inflammatory cells in the colon. Contact hypersensitivity was also exacerbated by C. albicans gut colonization, as demonstrated by increased swelling, myeloperoxidase activity, and proinflammatory cytokines in ear auricles. Furthermore, C. albicans gut colonization promoted limb joint inflammation in collagen-induced arthritis, in an animal model of rheumatoid arthritis. These findings suggest that C. albicans gut colonization in mice aggravates inflammation in allergic and autoimmune diseases, not only in the gut but also in the extra-gut tissues and underscores the necessity of investigating the pathogenic role of C. albicans gut colonization in immune diseases in humans.
20734542 Patients- and physicians- priorities for improvement. The case of rheumatic diseases. 2010 Apr OBJECTIVES: To compare the health priorities elected by patients with rheumatic diseases and by their attending rheumatologists. PATIENTS AND METHODS: We undertook a cross-sectional study among patients and rheumatologists in Portuguese rheumatology outpatient clinics. 75% of all Portuguese Rheumatology Departments agreed to participate. Rheumatologists from non-participating hospital departments were asked to collaborate through their private practices. All patients were eligible for inclusion except if they were under 18 years of age or had a mental disorder that would affect their participation. Data were collected through dedicated questionnaires. Patients were asked to indicate 3 priorities for improvement out of 12 health domains (Arthritis Impact Measurement Scale 2) regarding their rheumatic disease. Rheumatologists were asked similar questions focused around rheumatoid arthritis (RA) and osteoarthritis (OA). RESULTS: 1,868 patients and 56 rheumatologists entered the study. The most commonly selected priorities by patients with rheumatic diseases were: "Rheumatic pain" (70%), "Walking and bending" (45%), and "Hand and Finger Function" (40%). The main priority for improvement among patients with RA was "Rheumatic Pain" (69%), while rheumatologists more commonly elected "Work" (55%) as their main priority for these patients. Among patients with OA, "Rheumatic Pain" was the first priority for both patients and doctors (elected by 75%, and 55% of respondents, respectively). CONCLUSIONS: Our study showed discordance between the priorities for improvement elected by patients and by their respective physicians. This was more pronounced in RA than in OA. Studying and addressing such differences may support physicians and institutions to better achieve the prime goal of incorporating and responding to patients' needs and preferences.
19756659 [Recommendations on therapy using interleukin-1beta-blocking agents]. 2009 Nov In Germany, the only available interleukin-1beta (IL-1beta) blocking agent is anakinra (ANR) (as of August 2009) which is given subcutaneously at a dosage of 100 mg/day (adults) and 1-2 mg/kg body weight/day (maximum 100 mg/day) (children), respectively. Based on published data and clinical experience the German Society of Rheumatology (Deutsche Gesellschaft für Rheumatologie) recommends the following indications for ANR: (1) Rheumatoid arthritis, if treatment with two DMARDs (one of the two being methotrexate, MTX) for at least 6 months has failed. (2) Adult-onset and juvenile-onset Still's disease (systemic juvenile idiopathic arthritis) in the case of insufficient response to glucocorticoids or inadequate long-term dosage, as well as failure of a conventional DMARD, usually MTX. For both indications the treatment should be supervised and documented by a rheumatologist or paediatric rheumatologist. Cryopyrin-associated periodic syndromes (CAPS) are recommended as an additional treatment option for IL-1 blocking therapy. The efficacy of the fusion protein rilonacept (RIC) and the monoclonal antibody canakinumab in the treatment of CAPS has been proven by randomized, placebo-controlled trials. In the US, RIL was recently approved by the FDA for the treatment of CAPS under the "Orphan Drug Status".
19290936 PEST family phosphatases in immunity, autoimmunity, and autoinflammatory disorders. 2009 Mar The proline-, glutamic acid-, serine- and threonine-rich (PEST) family of protein tyrosine phosphatases (PTPs) includes proline-enriched phosphatase (PEP)/lymphoid tyrosine phosphatase (LYP), PTP-PEST, and PTP-hematopoietic stem cell fraction (HSCF). PEP/LYP is a potent inhibitor of T-cell activation, principally by suppressing the activity of Src family protein tyrosine kinases (PTKs). This function seems to be dependent, at least in part, on the ability of PEP to bind C-terminal Src kinase (Csk), a PTK also involved in inactivating Src kinases. Interestingly, a polymorphism of LYP in humans (R620W) is a significant risk factor for autoimmune diseases including type 1 diabetes, rheumatoid arthritis, and lupus. The R620W mutation may be a 'gain-of-function' mutation. In non-hematopoietic cells, PTP-PEST is a critical regulator of adhesion and migration. This effect correlates with the aptitude of PTP-PEST to dephosphorylate cytoskeletal proteins such as Cas, focal adhesion associated-kinase (FAK), Pyk2, and PSTPIP. While not established, a similar function may also exist in immune cells. Additionally, overexpression studies provided an indication that PTP-PEST may be a negative regulator of lymphocyte activation. Interestingly, mutations in a PTP-PEST- and PTP-HSCF-interacting protein, PSTPIP1, were identified in humans with pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome and familial recurrent arthritis, two autoinflammatory diseases. These mutations abrogate the ability of PSTPIP1 to bind PTP-PEST and PTP-HSCF, suggesting that these two PTPs may be negative regulators of inflammation.
19561096 Role of MAPK kinase 6 in arthritis: distinct mechanism of action in inflammation and cytok 2009 Jul 15 Development of p38alpha inhibitors for rheumatoid arthritis has been hindered by toxicity and limited efficacy. Therefore, we evaluated whether MKK6, an upstream kinase that regulates multiple p38 isoforms, might be an alternative therapeutic target in inflammatory arthritis. Wild-type (WT), MKK6(-/-), and MKK3(-/-) mice were administered K/BxN serum to induce arthritis. Articular expression of activated kinases and cytokines was determined by Western blot, qPCR, ELISA, and multiplex analysis. Immunoprecipitation and confocal microscopy experiments were performed to determine the subcellular location of MKK6, P-p38, and MAPKAPK2 (MK2). Arthritis scores were significantly lower in MKK6(-/-) mice compared with WT mice. Joint destruction and osteoclast differentiation were lower in MKK6(-/-), as were articular IL-6 and matrix metalloproteinase-3 expression. Phospho-p38 levels were modestly decreased in the joints of arthritic MKK6(-/-) mice compared with WT but were significantly higher than MKK3(-/-) mice. P-MK2 was low in MKK6(-/-) and MKK3(-/-) mice. Uncoupled p38 and MK2 activation was also observed in cultured, MKK6(-/-) FLS and confirmed using kinase assays. Immunoprecipitation assays and confocal microscopy showed that P-p38 and MK2 colocalized in activated WT but not MKK6(-/-) FLS. Distinct patterns of cytokine production were observed in MKK6(-/-) and MKK3(-/-) cells. MKK6 deficiency suppresses inflammatory arthritis and joint destruction, suggesting it might be a therapeutic target for inflammation. Although MKK3 and MKK6 activate the p38 pathway, they regulate distinct subsets of proinflammatory cytokines. MKK6 appears mainly to facilitate p38 and MK2 colocalization in the nucleus rather than to phosphorylate p38.
20861858 Association of EBF1, FAM167A(C8orf13)-BLK and TNFSF4 gene variants with primary Sjögren's 2011 Mar We performed a candidate gene association study in 540 patients with primary Sjögren's Syndrome (SS) from Sweden (n=344) and Norway (n=196) and 532 controls (n=319 Swedish, n=213 Norwegian). A total of 1139 single-nucleotide polymorphisms (SNPs) in 84 genes were analyzed. In the meta-analysis of the Swedish and Norwegian cohorts, we found high signals for association between primary SS and SNPs in three gene loci, not previously associated with primary SS. These are the early B-cell factor 1 (EBF1) gene, P=9.9 × 10(-5), OR 1.68, the family with sequence similarity 167 member A-B-lymphoid tyrosine kinase (FAM167A-BLK) locus, P=4.7 × 10(-4), OR 1.37 and the tumor necrosis factor superfamily (TNFSF4=Ox40L) gene, P=7.4 × 10(-4), OR 1.34. We also confirmed the association between primary SS and the IRF5/TNPO3 locus and the STAT4 gene. We found no association between the SNPs in these five genes and the presence of anti-SSA/anti-SSB antibodies. EBF1, BLK and TNFSF4 are all involved in B-cell differentiation and activation, and we conclude that polymorphisms in several susceptibility genes in the immune system contribute to the pathogenesis of primary SS.
19692434 Sjogren's syndrome myelopathy: spinal cord involvement in Sjogren's syndrome might be a ma 2009 Sep OBJECTIVE: To evaluate clinical characteristics, aquaporin (AQP)-4 antibody results, and probability of developing symptoms of neuromyelitis optica (NMO) in patients with Sjögren's syndrome myelopathy (SSM). METHODS: We identified eight patients with spinal cord involvement from 112 patients with Sjögren's syndrome (SS) referred to the neurology department. The clinical characteristics and AQP-4 antibody status, based on immunoprecipitation of EGFP-tagged AQP-4, of the patients with SSM were assessed. RESULTS: All patients with SSM had extensive spinal cord lesions, high mean annual relapse rates, and poor response to steroid treatment. Of the eight patients with SSM, seven patients satisfied the revised diagnostic criteria for NMO or showed positive results from AQP-4 antibody testing; one patient had incomplete follow-up. The clinical manifestations and AQP-4 autoantibody status of patients with SSM did not differ significantly from those of NMO patients without SS. CONCLUSION: All patients with SSM had poor prognosis with high mean annual relapse rates, and most seemed to have the clinical and immunological characteristics of NMO. Early aggressive immune therapies should be considered in patients with SSM irrespective of the presence or absence of optic neuritis.
20221662 Multiple dermatofibromas in a patient with systemic lupus erythematosus and Sjögren's syn 2010 Aug We report a case of multiple dermatofibromas in a patient with systemic lupus erythematosus (SLE) and Sjögren's syndrome. He was treated with prednisolone, diaphenylsulfone, and cyclosporine for SLE. He noticed two brown nodules on his right lower leg 3 years after the first consultation. Subsequently, six nodules developed within 6 months, and 2 more nodules after 10 months. Histopathological examination of a nodule on his left hand showed fibrotic proliferation with a storiform pattern in the whole dermis, but neither necrosis nor mitosis was observed. From these findings, a diagnosis of multiple dermatofibromas was made. As these tumors appeared during the remission stage of SLE, they might have been under immunosuppressive conditions caused by immunosuppressing agents rather than collagen disease itself.
19950301 Interleukin-12 induces salivary gland dysfunction in transgenic mice, providing a new mode 2009 Dec OBJECTIVE: Interleukin-12 (IL-12) is a pleiotropic cytokine that is elevated in the affected organs of patients with Sjögren's syndrome (SS). We have previously reported that overexpression of IL-12 in CBA mice leads to mononuclear infiltration of salivary and lacrimal glands, as well as to expansion of bronchial lymphoid tissue and decreased mucociliary clearance. Because xerostomia is one of the most important clinical features in SS patients, our main objective in the current study was to evaluate salivary gland function in IL-12-transgenic mice. Our secondary objective was to further characterize this animal model and to determine if the changes observed in these mice are representative of those observed in patients with SS overall. METHODS: Pilocarpine-stimulated salivary flow was used to address salivary gland function in a large group of IL-12-transgenic mice bred onto the autoimmune-prone SJL background. Furthermore, salivary glands were removed to assess the formation of infiltrates in the glands and gland morphology. Serum was also collected from these animals to investigate the formation of autoantibodies. RESULTS: Pilocarpine-stimulated salivary flow was significantly lower in IL-12-transgenic mice than in wild-type controls. Salivary glands from transgenic mice exhibited an increase in both the number and the size of lymphocytic foci, versus glands from age-matched controls. Furthermore, the acini in transgenic mice were fewer in number and larger in size compared with acini in controls. An age-dependent increase in anti-SSB/La antibodies was observed in IL-12-transgenic mice and was accompanied by an increase in antinuclear antibodies. CONCLUSION: Our findings indicate that a number of conditions associated with SS are exhibited by IL-12-transgenic SJL mice and that this model might be useful in researching multiple aspects of the disease.
19254127 Periodontal conditions of individuals with Sjögren's syndrome. 2009 Mar BACKGROUND: Sjögren's syndrome (SjS) is a systemic autoimmune disease that might lead to hyposalivation and negatively affect the oral environment. The evidence with regard to the periodontal conditions in this group of subjects is still controversial. This study aimed to evaluate the periodontal clinical conditions and inflammatory markers in gingival crevicular fluid (GCF) from patients with primary Sjögren's syndrome (SjS [P]) or secondary Sjögren's syndrome (SjS [S]) compared to a control group. METHODS: Nineteen individuals with SjS (11 SjS [P] and eight SjS [S]) and 19 controls, matched for gender, age, and tobacco exposure, were selected from two private clinics and a hospital. The groups were compared for stimulated whole saliva (SWS) flow rate, plaque index (PI), gingival index (GI), probing depth (PD), bleeding on probing (BOP), clinical attachment level (CAL), and total amount of interleukin (IL)-1beta and total elastase activity in the GCF. Generalized estimating equations were used for data analysis. RESULTS: Individuals with SjS had a significantly lower SWS flow rate and higher mean PI, GI, PD, CAL, and BOP than controls. After adjustment for plaque, GI remained significantly higher in patients with SjS. Patients with SjS (S) had significantly higher mean CAL and PD than patients with SjS (P), and CAL and BOP remained significantly higher in this subgroup after adjustment. No differences were observed with regard to the GCF inflammatory markers. After adjusting for PD, subjects with SjS (P) showed lower levels of IL-1beta compared to controls. CONCLUSION: SjS seemed to negatively affect the periodontal condition because gingival inflammation was more evident in the individuals with SjS, particularly those with SjS (S).
19196532 Sjögren's syndrome with ANCA-associated crescentic extramembranous glomerulonephritis. 2009 Mar A 49-year-old woman with a 1-year history of Sjögren's syndrome was diagnosed with cutaneous leukocytoclastic vasculitis and necrotizing crescentic membranous glomerulonephritis. Antineutrophil cytoplasmic antibodies targeting myeloperoxidase were found. She reported a transient episode of nephritis 4 years earlier. This pattern of kidney disease is not typical of Sjögren's syndrome. Methylprednisolone boluses followed by oral glucocorticoid therapy were given in combination with mycophenolate mofetil. Renal function stabilized after 2 months, and tests for anti-myeloperoxidase reverted to negative.
20661065 Clues for previously undiagnosed connective tissue disease in patients with trigeminal neu 2010 Aug BACKGROUND: Connective tissue diseases (CTD) may be associated with idiopathic trigeminal neuralgia (TN). The prevalence and diagnostic implications of this association are, however, not well established. OBJECTIVES: The objective of this study was to evaluate, in TN patients, if rheumatologic clinical and laboratory findings could contribute to the early diagnosis of rheumatic diseases. METHODS: Forty-six consecutive TN patients, 67% female, mean disease duration 8.78 +/- 7.25 years, and 47 controls were initially interviewed using a standard questionnaire based on common signs/symptoms of systemic lupus erythematosus, Sjögren syndrome, mixed CTD, and systemic sclerosis. Autoantibodies were detected by standard techniques. Those with rheumatologic complaints or positive autoantibodies were referred to the Rheumatology Outpatient Clinic for a more detailed evaluation. Secondary causes of TN were excluded. RESULTS: The frequency of Raynaud phenomenon (P = 0.026) and ANA reactivity (P = 0.04) were significantly higher in TN patients compared with controls. Fourteen TN patients were ANA positive. Seven of them reported concomitant rheumatic complaints, and interestingly, diffuse CTD was diagnosed in 4 (57%) of these patients: 1 systemic lupus erythematosus; 2 Sjögren syndrome; and 1 undifferentiated disease with scleritis and positive parotid scintigraphy. In all cases, TN preceded by at least 10 months the rheumatologic signs/symptoms. Moreover, these 4 TN patients with CTD had a higher frequency of sicca symptoms (P = 0.001) and higher titers of ANA (>or=1:320) (P = 0.006) than the remaining 42 TN patients without CTD diagnoses. Sixteen patients had isolated laboratory or clinical abnormalities, and none of them had CTD diagnoses. CONCLUSIONS: The concomitant presence of sicca symptoms and high titer ANA are clues for the early investigation of rheumatic diseases in TN patients.
20635899 Immunotherapeutic targets in estrogen deficiency-dependent Sjögren's syndrome-related man 2010 May Although a number of autoimmune diseases are known to develop in postmenopausal women, the mechanisms by which estrogen deficiency influences autoimmunity remain unclear. Previously, we found that tissue-specific apoptosis in the exocrine glands in estrogen-deficient mice may contribute to the development of autoimmune exocrinopathy. We found that RbAp48 overexpression induces p53-mediated apoptosis in the exocrine glands depending on estrogen deficiency. RbAp48-inducible transfectants result in rapid apoptosis with p53 phosphorylation (Ser9), and alpha-fodrin cleavage. Indeed, transgenic expression of the RbAp48 gene induced apoptosis in the exocrine glands, resulting in the development of autoimmune exocrinopathy resembling Sjögren's syndrome (SS). CD4(+) T-cell-mediated autoimmune lesions were aggravated with age, in association with production of autoantibodies against SS-A, SS-B and alpha-fodrin. These findings demonstrated that estrogen deficiency initiates tissue-specific apoptosis in the exocrine gland cells through RbAp48 overexpression and exerts a possible gender-based risk of autoimmune exocrinopathy in postmenopausal women. Thus, these data indicate RbAp48 to be a novel immunotherapeutic target for preventing epithelial cell apoptosis and the development of gender-based autoimmune exocrinopathy.
19833748 Autoantibodies and the risk of cardiovascular events. 2009 Nov OBJECTIVE: Inflammation and autoimmunity are associated with increased cardiovascular (CV) risk in patients with rheumatoid arthritis. This association may also be present in those without rheumatic diseases. Our purpose was to determine whether rheumatoid factor (RF), antinuclear antibody (ANA), and cyclic citrullinated peptide antibody (CCP) positivity are associated with increased risk of CV events and overall mortality in those with and without rheumatic diseases. METHODS: We performed a population-based cohort study of all subjects who had a RF and/or ANA test performed between January 1, 1990, and January 1, 2000, and/or CCP test performed between September 1, 2003, and January 1, 2005, with followup until April 1, 2007. Outcomes were ascertained using diagnostic indices from complete medical records, including CV events [myocardial infarction (MI), heart failure (HF), and peripheral vascular disease (PVD)] and mortality. Cox models were used to analyze the data. RESULTS: There were 6783 subjects with RF, 7852 with ANA, and 299 with CCP testing. Of these, 10.4%, 23.9%, and 14.7% were positive for RF, ANA, and CCP, respectively. Adjusting for age, sex, calendar year, comorbidity, and rheumatic disease, RF and ANA positivity were significant predictors of CV events [hazard ratio (HR) 1.24 and 1.26] and death (HR 1.43 and 1.18). Adjusting for age, CCP positivity was associated with CV events, but this association was not statistically significant (HR 3.1; 95% CI 0.8, 12.3). CONCLUSION: RF and ANA positivity are significant predictors of CV events and mortality in both those with and those without rheumatic diseases. These results support the role of immune dysregulation in the etiology of CV disease.
19934373 E2F-1-deficient NOD/SCID mice developed showing decreased saliva production. 2009 Dec The non-obese diabetic mouse (NOD) is the most characterized model used to study insulin-dependent type 1 diabetes mellitus (IDDM) and Sjoögren's syndrome (SS). In a previous report, we found NOD.E2f1(-/-) mice show a greater progressive development to IDDM and SS compared to NOD mice. Our previous data indicated a progressive decrease in regulatory T cells (CD4(+)CD25(+)) and a decrease in the systemic secretion systems for insulin, and saliva was associated with the progression of IDDM and SS. Therefore, to define the mechanism of early-onset IDDM SS in E2F-1 deficient NOD mice required further investigation by producing E2F-1 deficient NOD/SCID mice in which the T and B cells do not develop. The purpose here was to analyze the essential function of the E2F-1 molecule in the development of IDDM and SS; and the dysfunction of the pancreas islet and salivary gland in the NOD background using NOD/SCID mice. We produced NOD/SCID.E2f1(-/-) mice using homologous recombination; determined diabetes development; measured saliva and insulin production; and performed a histological analysis. The deficient mice showed a decreasing volume of saliva; no infiltration of lymphocytes into salivary glands; no development of diabetes; and no protein localization of FGFR-2b in the ducts of the salivary gland that regulates submandibular gland proliferation and morphogenesis. Therefore, we considered a deficiency in E2F-1 induces a decrease in regulatory T cells and an increase in auto-reactive T cells; however, the E2F-1 deficiency is not associated with T and B cells-independent dysfunction of pancreatic beta cell in insulin secretion. Further, the E2F-1 deficiency is associated with T and B cells-independent dysfunction of the salivary gland exhibits a decrease in saliva production volume. We suggest E2F-1 may be also associated with the differentiation of exocrine cells in the duct where FGFR-2b is expressed in the salivary gland. The E2F-1 deficient NOD/SCID mouse model is useful for showing the development of the salivary gland; and is also useful for various experiments in humanized mice.