Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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2463270 | Measurement of protein HC (alpha 1 microglobulin) and protein HC-IgA complex in different | 1988 Nov | Protein HC and protein HC-IgA complex were measured in 18 different types of fluid sample from healthy subjects and patients with different illnesses to determine if the concentrations of protein HC and protein HC-IgA complexes could be used to monitor certain diseases, when measured separately. The normal values for HC ranged from between 0.30 mg/l in saliva and 11.7 mg/l in blood plasma. HC-IgA complex has a greater range, from undetectable concentrations (urine, colostrum, and cervical mucus) up to 59.2 mg/l in blood plasma. Undetectable concentrations of HC-IgA complex were also shown in serum from patients with IgA immune deficiency and in cerebrospinal fluid from patients with multiple sclerosis. Increased concentrations of HC were noted in bronchoalveolar fluid from a patient with pulmonary alveolar proteinosis, serum from patients with Behcet's syndrome, and in synovial fluid from patients with gout, chondrocalcinosis, and rheumatoid arthritis. On the other hand, the concentrations of HC-IgA complex were raised only in those patients with pulmonary alveolar proteinosis or rheumatoid arthritis. | |
2106373 | The relationship between spinal trabecular bone mineral content and iliac crest trabecular | 1990 Mar | The relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume has been studied in 84 patients, 23 with primary osteoporosis, 19 with osteoporosis secondary to inflammatory bowel disease, and 42 with nonsteroid-treated rheumatoid arthritis. Spinal trabecular bone mineral density was measured in the first three lumbar vertebrae by quantitative computed tomography, and iliac crest trabecular bone volume was assessed histomorphometrically in sections from trans-iliac biopsies using computerized techniques. In all 84 patients, there was a significant positive correlation between the two measurements (r = 0.60, P less than 0.001). However, when the three patient groups were analyzed separately, a significant correlation was found in the group with secondary osteoporosis (r = 0.65, P less than 0.01) but not in the patients with primary osteoporosis (r = 0.07) or rheumatoid arthritis (r = 0.19). These results indicate that the relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume differs according to the underlying disease process, these differences possibly reflecting variations in skeletal patterns of bone loss in different types of osteoporosis. | |
2541162 | Impaired late suppression of Epstein-Barr virus (EBV)-induced immunoglobulin synthesis: a | 1989 Mar | We examined regulation of Epstein-Barr virus-induced plaque-forming cell generation in peripheral blood mononuclear cells from several autoimmune and seronegative diseases and correlated these results with Epstein-Barr virus-induced proliferation. We confirmed the defective regulation of Epstein-Barr virus-induced plaque-forming cells in peripheral blood mononuclear cells of patients with rheumatoid arthritis and scleroderma. Peripheral blood mononuclear cells from patients with seronegative arthropathies and chronic infective inflammation (cystic fibrosis) had normal regulation of Epstein-Barr virus-induced plaque-forming cells. Peripheral blood mononuclear cells from rheumatoid arthritis had excessive plaque-forming cell generation in the face of a normally regulated decrease in Epstein-Barr virus-induced proliferation. In contrast, peripheral blood mononuclear cells from scleroderma had defective suppression of both Epstein-Barr virus-induced proliferation and plaque-forming cell generation. Thus, impaired regulation of Epstein-Barr virus-induced plaque-forming cell generation is a common feature of autoimmune disease and demonstrates some specificity for these disorders. | |
3040599 | Antibody response against the Epstein-Barr virus-coded nuclear antigen2 (EBNA2) in differe | 1987 Sep 15 | Specific antibody responses against the 2 major subcomponents of EBNA, EBNA1 and EBNA2 were evaluated, in order to study whether this serological study was beneficial compared to classical EBV serology. During this investigation, 491 sera, obtained from blood donors and patients with Burkitt's lymphoma (BL), nasopharyngeal carcinoma (NPC), infectious mononucleosis (IM), Hodgkin's disease, renal transplantation, rheumatoid arthritis and Human Immunodeficiency Virus (HIV) infection, were tested. While the anti-EBNA1 response followed the classical anti-EBNA/Raji response (99% of anti-EBNA/Raji-positive sera also recognize EBNA1), the anti-EBNA2 response was much less frequent and did not correlate with either anti-EBNA/Raji or anti-EA antibodies. In a control population, 8% of individuals had antiEBNA2 antibodies at titers greater than or equal to 10. The percentage was 45% in NPC and 38% in EBV-associated BL; thus, although not detected in all patients with EBV-associated tumors, anti-EBNA2 serology might be a useful marker in BL and NPC. No antibody was detected in the early course of IM, but in rheumatoid arthritis and in HIV-infected patients, the percentage of positive individuals reached 54 and 68, respectively. Seroconversion to EBNA2 was noted in a few cases, including renal transplant recipients, AIDS patients, and complicated IM. This suggests that in these situations, EBNA 2 serology might represent a useful marker related to modulation of the immune status or EBV reactivation. | |
3014140 | Antibodies to type IV collagen in rheumatic diseases. | 1986 Apr | Rheumatic disease sera were examined by a sensitive and specific enzyme linked immunosorbent assay (ELISA) for antibodies to native and to denatured type IV collagen from basement membranes of bovine anterior lens capsules or human placenta. The frequency of antitype IV collagen antibodies depended on the antigen and the disease studied. No controls had human type IV collagen antibodies and only 5.6% had antibody to bovine type IV collagen. Antibody to one or more of our 4 antigens was seen in 20% of children with juvenile rheumatoid arthritis (JRA), 35% of patients with mixed connective tissue disease (MCTD), 40% of those with juvenile dermatomyositis (DM), 52% of adults with rheumatoid arthritis (RA), 56% of patients with scleroderma and 60% of patients with systemic lupus erythematosus (SLE). Antibodies to native human type IV collagen were rare (0-10%) except in SLE (45%). Antibodies to denatured human type IV collagen were commoner in RA, scleroderma and SLE. Antibodies to native bovine type IV collagen occurred in 8-20% of patient sera, and to denatured antigen in 25-26% of scleroderma, MCTD and DM patients. Antibovine type IV collagen activity measured by ELISA could be absorbed from positive sera by preincubation of the sera with bovine type IV collagen but not bovine type I collagen or native human placental type IV collagen, indicating that the antibodies were specific for bovine type IV collagen. | |
2906579 | Treatment of psoriatic arthritis with sulphasalazine: a one year open study. | 1988 Sep | Sulphasalazine (SASP) has recently become established as an effective treatment for active rheumatoid arthritis (RA), but has not previously been used in psoriatic arthritis in which remission-inducing drugs have proved disappointing. In this one year open study, 34 patients with active psoriatic arthritis were treated with sulphasalazine. An overall favourable clinical response was observed in 23 patients (67%). Nine patients (26%) achieved a very good therapeutic response and these either had arthritis associated with spondylitis or the symmetrical type of joint disease. Evaluation at 3, 6 and 12 months showed a significant improvement in inflammatory indices including a reduction in the C-reactive protein level and ESR. The drug was well-tolerated and side-effects were mild. Eight patients (23.5%) stopped the drug because of reactions and one patient with a rash was successfully desensitised. Fifty-three percent continued the drug into the second year. No apparent exacerbation of the psoriasis was observed. These results suggest that sulphasalazine is a safe and potentially effective drug in the treatment of psoriatic arthritis. A double-blind placebo-controlled trial has been set up to determine its true efficacy. | |
2053917 | Arthritis in patients infected with human T lymphotropic virus type I. Clinical and immuno | 1991 Jun | Ten patients with chronic inflammatory arthropathy and the human T lymphotropic virus type I (HTLV-I) are described. These patients showed chronic persistent oligoarthritis, associated with proliferative synovitis, in large joints. The place of birth or residence of these patients was within the area endemic for adult T cell leukemia (ATL) and HTLV-I. The age at onset of articular symptoms tended to be higher in these patients than in typical rheumatoid arthritis patients. Anti-HTLV-I antibodies were detected in both sera and synovial fluids from all patients. Western blot analysis revealed antibodies to viral gag proteins (p19, p24, and p28). Atypical lymphocytes with nuclear indentations, consistent with ATL-like cells, were observed in both synovial fluid and synovial tissue. Furthermore, HTLV-I proviral DNA was integrated into the DNA of synovial fluid cells and synovial tissue cells. These findings suggest that HTLV-I might be involved in the pathogenesis of this unique arthropathy. | |
2564781 | Requirements for flare reactions of joint inflammation induced in mice by cloned MT4+, Lyt | 1989 Mar | Joint inflammation was induced in C57B1/6 mice by injection of cloned MT4+, Lyt-2- T cells specific for the antigen methylated bovine serum albumin (mBSA), together with mBSA. In this model, after waning of the inflammation, flare reactions can be induced by a rechallenge with the specific antigen. Herein we show that such flare reactions can still be induced several weeks after waning of the joint inflammation, as was demonstrated both in normal C57B1/6 mice and in athymic C57B1 nude mice. The results in the latter group indicate that T cells of the recipient mice are not necessary for the elicitation of flare reactions. On histologic examination, the inflammatory infiltrates in the knee joints of the nude mice appeared to be mainly granulocytic. The cloned T cells persisted and remained functionally reactive in the knee joint for at least 2 weeks in the absence of the antigen, and thus, in the absence of inflammation. In view of the similarities between induced joint inflammation in mice and rheumatoid arthritis in humans, these data may be relevant to our understanding of the processes involved in the latter disease. | |
3266359 | Quantitative analysis of precursors frequency of rheumatoid factor (RF) producing human B | 1988 | Recently, a new culture system has been devised which leads to activation, proliferation and differentiation into antibody secreting cells of at least 90% of human peripheral blood B-lymphocytes. The system uses mutant EL-4 thymoma cells of mouse origin for B cell activation and T cell/macrophage supernatant as source of cytokines (L. Wen et al., Eur. J. Immunol. 17, 887, 1987). By an ELISA system with Fc fragments as antigen and the F(ab)2 fragment of antibodies against human IgM labelled with alkaline phosphatase, we analysed the frequencies of B cells producing IgM-RFs. The mean frequency of IgM-RF producing cells in normal controls was 1/3100 (s.d. = 0.2 log; n = 5) of circulating B cells. In 2 patients with seropositive rheumatoid arthritis (RA) the frequencies were higher (1/492; 1/262), but in 2 other seropositive patients a normal (1/5540) or even a decreased (1/20000) frequency was observed. The possible relation between circulating and synovial RF producing B cells is currently being investigated. | |
1863820 | Predictors of the long-term outcome of early synovitis: a 5-year follow-up study. | 1991 Aug | One hundred patients who presented to an Early Synovitis Clinic in 1979-81 were called for review after a minimum of 5 years. Sufficient data for analysis were obtained in 88 cases, of whom 36 had a final diagnosis of rheumatoid arthritis (19 seropositive, 17 seronegative) and 16 human parvovirus B19 arthropathy. Outcome was assessed by persistence of symptoms greater than 24 months and functional disability by Health Assessment Questionnaire. Sixty-two patients had persistent disease, with 26 showing some functional impairment (positive HAQ FDI). A number of presenting features were assessed for their ability to predict outcome at 5 years. Polyarticular onset of disease was associated with a poor prognosis but lacked both specificity and sensitivity. Certain laboratory tests at presentation, including positive rheumatoid factor and low serum sulphydryl levels, also indicated a poor outcome. Combining these serological abnormalities gave 100% specificity for detecting persistent, disabling disease but with rather low sensitivity. Thus, other test systems are required to increase further the successful prediction of clinical outcome in patients with early synovitis. | |
2322024 | Qualitative and quantitative expression of VHI associated cross reactive idiotopes within | 1990 Mar | Monoclonal rheumatoid factors (RFs) of the major Wa cross reactive idiotype group have been shown to express exclusively VKIII subgroup light chains and VHI subgroup heavy chains. A VKIII associated cross reactive idiotope (CRI) (17-109), however, was shown not to be exclusively expressed on IgM paraproteins having rheumatoid factor activity or to be present at increased levels in the sera of patients with rheumatoid arthritis (RA). Three VHI associated CRIs have been defined with monoclonal antibodies and quantitative studies of their representation are reported, together with VKIII, in IgM and IgM RF isolated from the sera of patients with early synovitis, some of whom progressed to classical RA. The results show (a) the probed CRIs were expressed predominantly on IgM RF rather than on non-RF IgM; (b) 5-10% of IgM RFs from patients with classical RA expressed the CRIs, but this represented a lower proportion of IgM RFs than observed for normal individuals or patients with self limiting synovitis; (c) VKIII light chains were highly associated with IgM RFs rather than non-RF IgM (75% and 25% respectively). It is suggested that the CRIs probed are markers for germline gene encoded antibodies or sequences resulting from minimal mutation of germline genes. The lowered proportion of RFs expressing CRIs in RA may therefore be evidence of polyclonal activation or specific antigenic stimulation, or both, resulting in maturation of the RF response with recruitment of further VH genes or extensive mutation of germline genes. These studies show that monoclonal RFs are relevant models of RF produced in RA and that the repertoire of RF autoantibodies may be encompassed within a small number of CRI expressing families. | |
2426054 | The use of synthetic peptides in the delineation of immunoglobulin antigenic epitopes and | 1986 | As an alternative strategy to the use of proteolytic and chemical cleavage in the production of fragments of immunoglobulins retaining Fc effector functions, peptides representative of amino acid sequences constituting the putative active sites have been synthesized and assessed for biological activity in various in vitro systems. This approach has been adopted in attempts to define more precisely the autoantigenic epitope on human IgG against which anti-gamma-globulin antibodies (the so-called general 'rheumatoid factors'), found in the sera and joint fluids of patients with rheumatoid arthritis, are directed. Synthetic peptides representative of epsilon-chain sequences are being used in the production of antibodies (polyclonal and monoclonal) directed against specific epitopes within the Fc regions of human and rat IgE. The ability of these antisera to influence the in vitro functional properties of IgE anaphylactic antibodies is now under investigation, with particular attention being focused on cytophilicity and mast cell triggering. Preliminary findings suggest that certain of the antisera might be capable of inhibiting mast cell sensitization by IgE antibodies, and therefore might form the basis of a new type of anti-allergy compound. | |
1696860 | Prevention of adjuvant arthritis in rats by a nonapeptide from the 65-kD mycobacterial hea | 1990 Aug | Adjuvant arthritis in Lewis rats is a model of T cell-mediated autoimmune arthritis resembling human rheumatoid arthritis. A nonapeptide from the 65-kD heat-shock protein of Mycobacterium bovis BCG, amino acid sequence 180-188, has been described to carry the dominant immunogenic epitope(s) for both arthritis-protective and arthritogenic T cell clones. Here we demonstrate that immunizations with the synthetic nonapeptide completely protected rats against adjuvant arthritis induced by M. tuberculosis. Interestingly, deletion of the N-terminal threonine of the nonapeptide resulted in loss of the protective activity. Pretreatments with the nonapeptide resulted in an immune response to the nonapeptide and to M. tuberculosis. After immunizations with the synthetic nonapeptide, only low titres of nonapeptide-specific antibodies were produced, whereas a significant cellular immune response to the nonapeptide was observed. In addition, the protection was transferable to naive rats by spleen T cells. These findings document the requirement of a T cell-specific immune response to the dominant epitope of the 65-kD mycobacterial heat-shock protein for the protection against adjuvant arthritis and suggest the feasibility of immune intervention in autoimmune arthritis through the use of synthetic peptides. | |
2639111 | Orofacial manifestations in the rheumatic diseases. | 1989 Jul | Rheumatic diseases will often affect the temporomandibular joint, but other orofacial tissues may also show manifestations. This article, based on a lecture given at the Royal National Hospital for Rheumatic Diseases, Bath, is intended to help the dental practitioner recognize and treat these symptoms. | |
2204601 | [Chronic conjunctivitis]. | 1990 May 30 | The etiology, clinical picture, diagnosis and treatment of chronic inflammatory diseases of the conjunctiva are described. It is emphasized that, despite the respective specific etiology, the symptomatology has common factors, treatment is difficult and all too often only symptomatic, and chronic inflammatory diseases of the conjunctiva sooner or later lead to the so-called dry eye syndrome. | |
3075075 | Modulation of human natural killer cell function by cytokines and rheumatic disease. | 1988 | The activity of natural killer (NK) cells can be modified by a number of factors that either increase or suppress cytotoxicity. We have investigated in detail the cytokine induced killing of a NK resistant renal carcinoma cell line Cur by human NK cells. Preincubation of peripheral blood mononuclear cells with interferon alpha (IFN alpha), interleukin 2 (Il-2), interleukin 1 (Il-1) and tumor necrosis factor alpha greatly increased the rate and magnitude of Cur killing. Positively selected CD16 (+) cells were found to respond to cytokine stimulation and to mediate Cur killing. The effects of Il-2 and IFNa could be upregulated by costimulation of effector cells with Il-1 or TNF alpha. It was shown that TNF alpha induced Il-2 receptor expression on CD16(+) cells alone and even more in combination with Il-2. Studies of NK cell function in various rheumatic diseases revealed reduced NK cytotoxicity in peripheral blood and synovial fluid (SF), both in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA). By contrast, normal NK function was found in patients with ankylosing spondylitis (AS) and psoriatic arthritis. A discordance with regard to the percentage of Leu 7 positive mononuclear cells and NK function in peripheral blood and SF was demonstrated. Minimal expression of Leu 7 positive cells and cytotoxicity was present in synovial membranes. NK function in rheumatic disease was largely independent of drug therapy. Natural killer (NK) cells are a subset of lymphocytes that mediate spontaneous cytotoxicity against certain tumor and virus infected cells without any known prior sensitation.(ABSTRACT TRUNCATED AT 250 WORDS) | |
1766493 | Serum IgA class anti-IgA antibody in IgA nephropathy. | 1991 | IgA class anti-IgA antibody was sought by an immunoabsorbent technique in sera from patients with IgA nephropathy (IgA-N, n = 62), other forms of primary glomerulonephritis (PGN, n = 41), seropositive rheumatoid arthritis (RF-positive, n = 18) and normal controls (c, n = 50). IgA-N (31%) and RF-positive (56%) patients showed a significant increase in IgA anti-IgA antibody levels. The subclass of IgA anti-IgA antibody was predominantly IgA1 in both IgA-N and RF-positive patients. Size analysis revealed the dimer/monomer ratio to be significantly increased in IgA-N patients compared with that of RF-positive patients (p = 0.03). These results indicate the possible existence of the dimeric form of IgA class anti-IgA antibody in the circulation of IgA-N patients. | |
2066940 | C-reactive protein as an index of disease activity. Comparison of tenidap, cyclophosphamid | 1991 Apr | C-reactive protein (CRP) concentrations are a useful plasma protein measure that correlate with disease severity and radiographic progression in rheumatoid arthritis (RA). We compared 3 drugs with different mechanisms, i.e., tenidap, dexamethasone and cyclophosphamide, on both CRP levels and soft tissue swelling in the rat adjuvant arthritis model. CRP rose from a normal concentration of approximately 400 micrograms/ml during the first phase of adjuvant arthritis to approximately 1200 micrograms/ml (primary response), then fell to approximately 900 micrograms/ml and rose again as the disease became systemic during the secondary response to approximately 1400 micrograms/ml. When treatment was administered prophylactically, tenidap and dexamethasone suppressed both the primary and secondary CRP and swelling responses. Cyclophosphamide was without effect in the primary response, but inhibited both swelling and CRP in the secondary response. When therapeutic treatment was begun after secondary disease was established, only tenidap and dexamethasone inhibited CRP and swelling. Both dexamethasone and cyclophosphamide decreased lymphocyte numbers during treatment whereas lymphocyte numbers were elevated during tenidap treatment, suggesting a different mechanism of action for tenidap. CRP levels were more closely linked to the rate of change of paw swelling (disease progression) than to paw volume. | |
2526867 | Family resources as resistance factors for psychological maladjustment in chronically ill | 1989 Jun | The hypothesis that their psychological adjustment is related in part to resources present in their families was investigated in 153 children, age 4-16, who had one of five chronic physical disorders: juvenile diabetes, juvenile rheumatoid arthritis, chronic obesity, spina bifida, or cerebral palsy. Their mothers completed standardized psychometric instruments to measure specific dimensions of family psychological and utilitarian resources and of child adjustment. Variation in children's psychological adjustment was related both to their psychological and utilitarian family resources. Psychological family resources contributed uniquely to the prediction of adjustment beyond that provided by utilitarian family resources. These results are discussed as having implications for the identification of chronically ill and handicapped children at risk for adjustment difficulties. | |
2878644 | Serum and synovial fluid levels of angiotensin converting enzyme in polyarthritis. | 1986 Nov | Serum levels of angiotensin converting enzyme (ACE) activity in patients with rheumatoid arthritis (RA) (n = 48), osteoarthritis (OA) (n = 11), ankylosing spondylitis (n = 24), psoriatic arthritis (n = 12), and Behçet's syndrome (n = 20) were not significantly different from those of normal controls (n = 26). Synovial fluid ACE activity was lower in OA than in RA but was similar when corrected for protein levels. An increase in serum ACE concentration in patients with RA receiving captopril therapy is in agreement with previous results. There was some correlation of ACE with erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) but not with clinical indices in captopril treated patients. It is suggested that the beneficial actions of captopril in the treatment of RA are not due to its activity as an ACE inhibitor, but more probably a result of captopril being an aliphatic thiol. |