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

ID PMID Title PublicationDate abstract
8866754 Effect of mizoribine on collagen-induced arthritis in mice. 1996 Feb This study examines the effect of mizoribine (MZR), an immunosuppressant, on collagen-induced arthritis in mice. DBA/1J mice, immunized on days 0 and 21 with 200 micrograms of type II collagen in complete Freund adjuvant, were treated with various doses of MZR for 12 weeks, beginning on the day after the primary immunization. MZR reduced the arthritis score in a dose-dependent fashion, showing significant suppression, even at a dose of 10 mg/kg. At doses of more than 20 mg/kg, MZR also significantly suppressed bone damage in the hind limbs. MZR significantly suppressed the delayed-type hypersensitivity response to type II collagen, but only slightly decreased anti-type II collagen antibody levels. MZR restored the L3T4+/Lyt-2+ ratio, which was increased in arthritic mice, to the level found in normal mice. These findings show that MZR suppresses collagen-induced arthritis and bone damage in mice, and suggest that the inhibitory effect of MZR is based on its suppression of cellular immunity. These results provide a theoretical basis for the clinical use of MZR in rheumatoid arthritis.
8003617 Analysis of the V kappa III variable regions of polyclonal rheumatoid factors arising duri 1993 The mechanisms that govern autoantibody production are still under debate. In particular, auto-antibodies can appear as a consequence of a polyclonal activation of B cells or as a consequence of an antigen driven B cell expansion. The molecular analysis of the variable regions of auto-antibodies arising during different clinical situations can help to understand the origin of auto-antibodies. We recently described the main light chain variable regions of polyclonal rheumatoid factors occurring during rheumatoid arthritis and suggested that the mutation pattern of these regions could reflect an antigen driven process. Using the same approach, we now report the molecular analysis of the same light chain variable region containing a VKIII segment of rheumatoid factors originating from a polyclonal activation of B cells during an in vivo Epstein-Barr virus infection, infectious mononucleosis. The cDNA derived from rheumatoid factor synthetizing cells were amplified by two sets of polymerase chain reaction. The amplified products were cloned in M13mp19 phages and sequenced. The nucleotide analysis of the VKIII containing VK regions shows that: 1) the rheumatoid factor activity is associated with the 3 VKIII genes (Kv 325, Kv 328 and Vg) already known to encode for monoclonal and polyclonal rheumatoid factors, 2) there is a preferential use of Kv 328 and Vg, each one of these genes being poorly mutated, 3) the CDR mutation rates of these genes is no higher than the framework mutation rates, 4) there is a restriction of the JK usage; Kv 328 derived gene segments rearrange exclusively with JK1, Vg preferentially rearranges with JK1 and JK4. These results mainly suggest that naturally occurring polyclonal activation of autoreactive B cells produces poorly mutated autoantibodies.
9121094 [Olifen action on mutagenesis in human lymphocytes]. 1996 Antihypoxic drug olifen has been studied for effect in 72-hour PHA-stimulated cultures of blood lymphocytes in 15 healthy donors and 35 patients with diseases accompanied by enhanced mutagenesis in lymphocytes (rheumatoid arthritis, systemic lupus erythematosus, hypophyseal adenoma, neoplasms, chronic intoxications). Olifen has no mutagenic effect on mutagenesis in lymphocytes in a wide dose range. In diseases with intensive mutagenesis in lymphocytes olifen exhibits antimutagenic effect without lymphopoiesis.
7959641 The arteritides. 1994 Jul This article reviews the histopathological, clinical and immunological features of the arteritides. Based on these criteria, a classification scheme is proposed that includes infectious and non-infectious causes. Included in the non-infectious arteritides are: hypersensitivity vasculitis including serum sickness. Henoch-Schönlein purpura, mixed cryoglobulinaemia, hypocomplementaemia, drug and malignancy-associated vasculitis; arteritides of small and medium-sized arteries including polyarteritis nodosa, Kawasaki's disease, Wegener's granulomatosis, Churg-Strauss syndrome, necrotizing sarcoid granulomatosis, thromboangiitis obliterans (Buerger's disease) and localized forms of arteritis; arteritides involving large, medium and small-sized arteries which includes giant cell (temporal) arteritis, Takayasu's disease and arteritis of collagen-vascular disease (rheumatoid arthritis, rheumatic fever, Behçet's disease, Sjörgren's syndrome, systemic lupus erythematosis and systemic sclerosis.
8690467 Transfer of type II collagen-induced arthritis from DBA/1 to severe combined immunodeficie 1996 Jun Collagen-induced arthritis in susceptible mice is widely accepted as an experimental model for human rheumatoid arthritis (RA). We have investigated the role of the Mac-1 integrin beta 2 in the development and maintenance of arthritis by means of in vivo administration of 5C6 monoclonal antibody (mAb) to block this receptor. Injection of a single dose of 5C6 mAb (0.5 mg, intraperitoneally) prior to the expected onset of collagen-induced arthritis in DBA/1 mice diminished the severity of subsequent disease in these animals, as assessed both clinically and histologically (P < 0.01, chi 2). In the DBA/1 to severe combined immunodeficiency (SCID) transfer model of arthritis, the incidence of clinical arthritis was significantly reduced in SCID mice receiving maintained 5C6 treatment commencing the day prior to administration of donor splenocytes. Histological evaluation of joints from animals without clinically evident arthritis confirmed the absence of an inflammatory infiltrate in 22/27 joints examined. In a minority of these joints, however, synovial hyperplasia was apparent. In contrast, delaying antibody administration until 10 days after donor spleen cell transfer failed to protect three of five SCID recipients. These results confirm a functional role for Mac-1 in the generation of collagen-induced arthritis in mice. Since mAb 5C6 is non-cytotoxic, its action must be by blockade of the interactions between Mac-1 and its natural ligand(s). Our findings support the hypothesis that cells expressing Mac-1 play an important role in the induction and maintenance of joint damage in collagen-induced arthritis.
7736958 [Severe pneumonitis as a complication of low-dose methotrexate therapy in psoriasis-associ 1995 Apr 28 A 71-year-old woman with psoriasis-associated rheumatoid arthritis had for 15 months been treated with methotrexate (5 mg/week orally). Four weeks before admission she had developed dyspnoea and cough. On admission her axillary temperature was 38.2 degrees C, the white cell count was normal. Erythrocyte sedimentation rate (50/90 mm), lactate dehydrogenase activity (449 U/l) and the creatinine level (1.33 mg/dl) were all elevated. Blood gas analysis revealed partial respiratory impairment (pO2 52 mm Hg), and the chest X-ray demonstrated bilateral interstitial-alveolar changes. Despite antibiotics the temperature continued to rise, and on the 11th day a blood eosinophilia of 4% was noted. The bronchial mucosa was normal on bronchoscopy, and transbronchial biopsy showed only minor interstitial fibrosis, occasional macrophages and lymphocytes. Cultures of the lavage-fluid were negative. As methotrexate pneumonitis was suspected the drug was discontinued and prednisolone administered (50 mg daily for 3 days, gradually reducing over 7 days). The symptoms quickly improved, and blood gas analysis and the X-rays became normal. The patient was discharged symptom-free after 30 days.
7808939 [Results of surgical treatment for tennis elbow]. 1993 Jul 19 This paper presented results after operative treatment of tennis elbow in 32 patients. I have done such types of operations; Froimson (14), Spencer and Herndon (8), Bosworth-Boyd (7) and Froimson with elbow joint synovectomy and radial head resection (3). In young people best results I obtained after Froimson operation. Results of operative treatment of the tennis elbow are dependent on systemic disease. The worst results I obtained in rheumatoid arthritis.
7807148 Motor neurone disease associated with several immunological disorders: a case report. 1994 Jul A 44-year-old woman developed rheumatoid arthritis, pemphigus vulgaris and myasthenia gravis. Motor neurone disease appeared 2 years later. Hashimoto's thyroiditis was diagnosed after a severe stress in the autumn of 1991.
8994869 Cytokines in autoimmunity. 1996 Dec The past few years have witnessed exciting developments regarding the role of cytokines in autoimmune diseases, particularly in rheumatoid arthritis and Crohn's disease, with the demonstration that anti-TNF alpha therapy is clinically beneficial and provides reproducible results. Recent contributions to this field, derived from in vivo studies in animal models of autoimmunity, and increasingly from clinical trials, have greatly enhanced our understanding of this field.
1393233 Rheumatology and the gut. 1992 Oct 7 Some conditions may present with gastrointestinal and rheumatological manifestations. Salmonella osteomyelitis results from direct infection of bone following gut infection and bacteraemia, but in other conditions the pathogenesis is less clear. There may be a microbial cause for rheumatoid arthritis; however, this theory remains unproven.
7919694 Connective tissue diseases. 1994 The connective tissue diseases are musculoskeletal disorders that have an autoimmune basis. They can affect the internal organ systems and may have numerous ocular manifestations. This chapter discusses both the systemic and ocular findings of certain connective tissue diseases, specifically cranial arteritis, Sjögren's syndrome, rheumatoid arthritis, scleroderma, and lupus erythematosus. Treatment for the clinical manifestations of each disease is also reviewed.
1517488 Erythema annulare centrifugum associated with gold sodium thiomalate therapy. 1992 Aug Two women with rheumatoid arthritis developed erythema annulare centrifugum while receiving gold thiomalate therapy. Both patients had similar clinical and histologic findings. Results of a lymphocyte stimulation test were positive in one patient but not in the other.
8026530 Expression of a transgenic class II Ab gene confers susceptibility to collagen-induced art 1994 Jul The major histocompatibility complex (MHC) class II region is assumed to influence autoimmune diseases such as rheumatoid arthritis. In the mouse, the H-2q haplotype is associated with susceptibility to collagen-induced arthritis, while the H-2p haplotype is not. The class II A molecules of these haplotypes differ by only four amino acids in the first domain of the beta chain. To test if this difference accounts for the MHC influence on susceptibility to collagen-induced arthritis, H-2p mice were made transgenic with an Abp gene altered to resemble the Abq gene. The transgenic A beta chain hybridized with the A alpha p chain and was shown to be physiologically expressed by testing antigen-presentation capacity to Aq-restricted T cell hybridomas and with FACS analyses. These transgenic mice developed an autoimmune response to type II collagen and also collagen-induced arthritis. The data unequivocally suggest the Ab gene as a major genetic susceptibility locus for autoimmune collagen-induced arthritis.
1381980 Cartilage oligomeric matrix protein: a novel marker of cartilage turnover detectable in sy 1992 Sep Cartilage oligomeric matrix protein (COMP) is a tissue specific non-collagenous matrix protein. We have developed an enzyme-linked immunosorbent assay for the detection of this protein in synovial fluid and serum. The protein has been quantified in these fluids in patients with rheumatoid arthritis (RA), reactive arthritis, juvenile chronic arthritis, osteoarthritis and in sera of control subjects. The protein was detectable in all fluids and the synovial fluid levels were always higher than in serum in paired samples. The highest knee joint synovial fluid levels were found in reactive arthritis patients and the lowest in RA patients with advanced destruction of the knee joint. However, the relative synovial fluid content of COMP was higher in these RA patients than in patients with advanced osteoarthritis. In patients with long-standing reactive synovitis the concentrations decreased. This decrease, however, was less marked than for proteoglycan concentrations. The serum concentrations were low in patients with juvenile chronic arthritis and in patients with RA with advanced cartilage destruction of the studied knee joint. In the other groups serum levels did not differ between groups or from controls.
7724996 Serum IL-4, IL-10 and IL-6 levels in inflammatory arthritis. 1995 As the available in vitro and in vivo data suggest that interleukin (IL)-4 and IL-10 have immunosuppressive activity, our hypothesis was that serum IL-4 and IL-10 levels would correlate inversely with parameters of inflammation in patients with inflammatory arthritis. IL-4 was detected in the serum of 12 out of 140 patients with rheumatoid arthritis (RA), which was increased compared to the proportion found with patients with osteoarthritis (OA; P < 0.02). In addition, IL-4 was detected in the serum of 2 of 19 patients with systemic lupus erythematosus (SLE), 2 of 24 patients with psoriatic arthritis and 1 of 5 patients with Behçet's syndrome. No IL-4 was detected in patients with the following conditions: OA (58 patients), gout (17 patients), ankylosing spondylitis (6 patients), Reiter's syndrome (6 patients), polymyalgia rheumatica (6 patients), temporal arteritis (5 patients) and scleroderma (3 patients). No IL-10 was detected in any of the sera tested. We discuss the possible relevance of these results to the regulation of the immune response evident in inflammatory arthritis.
7767341 Development of anti-Sm and anti-DNA antibodies followed by clinical manifestation of syste 1995 Feb A 69-year-old Japanese women who had been followed up for 10 years as a primary Sjögren's syndrome, is reported. She suddenly developed serological and clinical characteristics of systemic lupus erythematosus (SLE): anti-Sm and anti-dsDNA antibodies followed by nephrotic syndrome and pancytopenia. This case suggests that the diagnosis of primary Sjögren's syndrome should be considered as tentative in certain cases and that the development of serological characteristics precede and are associated with the development of clinical symptoms of SLE.
8190294 Anti-Ro(SS-A) autoantibodies in central nervous system disease associated with Sjögren's 1994 May OBJECTIVE: To examine in Sjögren's syndrome (SS) the interrelationship between the presence of the anti-Ro(SS-A) antibody response and (1) concomitant presence and type (ie, focal or nonfocal) of CNS disease (CNS-SS), (2) cross-sectional brain MRI or CT, and (3) abnormal cerebral angiography. METHODS: Neurologic, neuroimaging, and angiographic features of CNS-SS patients were correlated with the presence of precipitating anti-Ro(SS-A) autoantibodies detected by gel double-immunodiffusion or quantitative ELISA, which detects antibodies directed against the 60-kd peptide. Statistical analyses were performed using Fisher's exact test (two-tailed) with Haldane's adjustment and odds ratio with Cornfield 95% confidence intervals. RESULTS: Precipitating antibodies against the Ro(SS-A) antigen, determined by gel double-immunodiffusion, were present in an increased frequency in CNS-SS patients with (1) documented clinical CNS disease, (2) focal clinical CNS manifestations and serious complications, (3) large regions of increased signal intensity, consistent with ischemia/infarcts on brain MRI scans or regions of decreased attenuation consistent with infarcts on CT, and (4) abnormal cerebral angiograms consistent with small-vessel angiitis. Finally, the anti-Ro(SS-A) antibody response in CNS was directed against the 60-kd peptide specificity, determined by ELISA. CONCLUSIONS: Clinical, neuroimaging (cerebral CT), and angiographic observation suggest that a subset of anti-Ro(SS-A) antibody-positive, in contrast with -negative, CNS-SS patients have more serious and extensive CNS disease, some with frank cerebral angiopathy. Anti-Ro(SS-A) antibodies are postulated to play a role in mediating or potentiating vascular injury in CNS-SS.
8339128 Progression of sialadenitis in Sjögren's syndrome. 1993 Jul An analysis of progression of sialadenitis in patients with primary and secondary SS has been performed. For this purpose patients were prospectively followed and evaluated with respect to stimulated whole salivary secretion and morphology of labial salivary gland biopsies. Twenty-one patients with primary SS and 18 with secondary SS were followed for a mean of 39 +/- 20 months (range 11-112 months). During this observation period the lymphocytic infiltration in minor salivary glands, measured as focus score, increased in 14/21 (67%) patients with primary SS and in 14/18 (78%) patients with secondary SS. Altogether there was a statistically significant increase in focus score in both primary and secondary SS, but no reduction in salivary production. Consequently, no correlation between changes in focus score and stimulated salivary secretion was found in either primary or secondary SS.
8702455 Development of complete heart block in an adult patient with Sjögren's syndrome and anti- 1996 Aug We describe the occurrence of complete heart block in a patient with Sjögren's syndrome. The patient's serum contained antibodies to both the 60-kd and 52-kd Ro proteins. This case indicates that although the adult atrioventricular node may be relatively resistant to the development of anti-Ro-associated heart block, it can nevertheless be affected.
9005667 [The normal tear fluid and decreased tearing in patients with Sjögren's disease and Sjög 1996 Mar Studies of total proteins, lysozyme and glucose in 25 patients (50 eyes) with Sjogren's disease and 26 patients (52 eyes) with Sjogren's syndrome have revealed a statistically significant reduction of tear production in patients vs. the normal subjects. The results obtained can be used both for diagnostic and therapeutic, purposes, in particular for dry-eye patients.