Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 3127092 | Detection of activated T cell products in the rheumatoid joint using cDNA probes to Interl | 1988 Feb | Attempts to detect immune mediators in RA synovial fluids by bioassay or radioimmunoassay have yielded conflicting results, and so we have begun to analyse the complex immunological reactions occurring within the rheumatoid joint using recombinant DNA technology. High levels of Interleukin-2 (IL-2) and IL-2 receptor transcripts were found in the mononuclear cells of the rheumatoid lesions. Interferon gamma (IFN gamma) mRNA was also detected, although at lower level than IL-2. To investigate the possible relevance of IL-2 and IL-2 receptor mRNA expression to the chronicity of the disease, RA joint cells were cultured in the absence of any stimulus, and the duration of mRNA expression compared to that of blood mononuclear cells (PBM), optimally stimulated. IL-2 mRNA was found to persist in culture for many days, in contrast to its transient (less than 24 h) presence in stimulated PBM. IL-2 receptor expression was also prolonged. In contrast IFN gamma mRNA, present at biopsy in 10/12 RA samples, was found to increase significantly in vitro. These results suggest that persistent T cell activation is of importance in the pathogenesis of RA, and suggests that prolonged mediator production (IL-2 and IFN gamma) may be of importance. The elevation of IFN gamma mRNA in culture and its lower relative expression suggests that there are inhibitory immunoregulatory influences within the RA joint. To determine whether abnormal IL-2 mRNA expression may be due to a genetic defect in the region controlling IL-2 gene expression, Southern blotting analysis of genomic DNA was performed with a 5' flanking probe using normal, RA and systemic lupus erythematosis patients. No abnormalities were detected. | |
| 2693162 | Effect of ranitidine on gastroduodenal mucosal damage in patients on long-term non-steroid | 1989 | Twenty-four patients taking long-term non-steroidal anti-inflammatory drugs (NSAIDs) were followed in a double-blind placebo-controlled trial to assess the effect of ranitidine 300 and 600 mg daily on upper gastrointestinal mucosal damage and to assess methods of monitoring mucosal damage. Sixteen were given ranitidine and 8 had placebo throughout the study. Comparisons suggested that ranitidine reduced symptoms and endoscopic evidence of mucosal damage. Histological evidence of gastritis was present in only half of those on ranitidine but in all receiving placebo. Erosions and blood loss occurred intermittently during the study but faecal blood losses using 51Cr-labelled red cells failed to identify any difference between groups. Endoscopic observation of erosions and serial biopsies may provide simple, reliable measurements for future studies to assess the effect of therapy in reducing mucosal damage from long-term NSAIDs. | |
| 3498594 | A new assay for anti-DNA antibodies in serum which includes the measurement of anti-Z-DNA. | 1987 Aug | A simple, rapid assay for measuring anti-DNA titre of serum which includes anti-Z-DNA is described. The assay involves solution binding of antibody to labelled DNA under conditions such that the DNA is altered to form a left-handed or Z-DNA structure in the presence of cobalt ions. The absence or presence of cobalt determines a B or Z form structure in DNA and antibodies to these forms are detectable. The majority of SLE and RA patients (88%) have a higher anti-DNA titre in the presence of cobalt ions. An additional 25% of SLE patients and 22/23 RA patients who had normal anti-DNA levels according to the Crithidea assay, reacted with abnormal titres in our assay. Patients experiencing a relapse in SLE also showed a large increase in anti-DNA in the presence of antigenic Z-DNA. These results suggest that monitoring anti-DNA levels in SLE and RA to detect anti-Z DNA antibodies, provides significant advantages over methods currently in use to measure anti-DNA antibodies. | |
| 3254049 | Morphological diversity of DRC-1 positive cells: human follicular dendritic cells and thei | 1988 | Follicular dendritic cells (FDC) and their relatives of the human tonsils and lymph nodes were immunoelectron microscopically analyzed with a monoclonal antibody DRC-1 (DAKO) in a combination with an enzymatic isolation technique. DRC-1+ cells were largely grouped into three type A (large mono- to multinucleated, sea anemone-fashioned, bearing labyrinth structures, in germinal center), type B (oligodendritic or stellate, medium-sized, in the corona and the primary follicle) and type C (individually located, medium-sized. lymphoid cell-fashioned, outside follicles). Type C were found in hyperplastic lymphoid tissue as well as in some granulation tissue. The DRC-1+ mononuclear cells were curiously encountered in the peripheral blood of some autoimmune disease patients in contrast with no identification in healthy persons. Furthermore some DRC-1+ cells obtained from autoimmune patient were confirmed to proliferate in culture. | |
| 2786978 | Induction of anticentromere antibody in patients receiving treatment with D-penicillamine. | 1989 May 15 | Anticentromere antibody (ACA) was previously described as a specific marker for CREST, progressive systemic sclerosis (PSS), scleroderma (SCL), Raynaud's phenomenon (RP) and primary biliary cirrhosis (PBC). In this present investigation ACA was observed appearing and disappearing due to D-penicillamine (DPA) treatment in 7 patients without any features of CREST, PSS, SCL, RP or PBC. HLA-DR3 was found in 5/7 of these patients. DPA induced ACA should be added to adverse immunologic drug reactions. | |
| 3495454 | [Assessment of the effect of prospidin and cyclophosphane on the indices of the T and B im | 1987 Mar | Prospidin was shown to produce a decrease of receptors on T- and B-lymphocytes and T-subpopulations, to inhibit migration of leucocytes under the influence of the antigenic stimulus, to reduce the cytopathic activity of lymphocytes and the level of secreted immunoglobulins of the main classes. The degree of prospidin immunodepressive effect is compared with that of cyclophosphane. | |
| 3735276 | Current practice in antimalarial drug prescribing in rheumatoid arthritis. | 1986 Jun | An analytic mail survey was conducted among Canadian and Australian rheumatologists to probe current prescribing practices for antimalarial agents. Ninety-six percent of respondents prescribed antimalarial therapy for rheumatoid arthritis with a preference for the use of hydroxychloroquine. The most frequently reported risk estimates for serious retinal toxicity were 0.01 and less than or equal to 0.001. Seventy-eight percent of rheumatologists reported 1 to 50% of patients refusing antimalarial therapy, usually because of concern regarding ocular toxicity. Our study indicates the importance of presenting the relevant risk:benefit data in an accurate and comprehensible form to potential recipients. | |
| 2150801 | [Studies on HLA-B27 and T-cell subsets in patients with endogenous anterior uveitis]. | 1990 Sep | 37 (37%) of 100 patients with anterior uveitis were found HLA-B27 positive (5.3% in the normal controls); 35 (94.6%) of the 37 cases were nongranulomatous and 78.0% were associated with various types of arthritis. T-cell subsets in periphery circulation were evaluated in 47 anterior uveitis patients and 18 controls by means of monoclonal antibodies. Patients with active anterior uveitis had less OKT3+ cells than patients in the inactive phase; there were more OKT4+ and OKT8+ cells in patients in the active phase than in the controls, and particularly the OKT8+ cells were more than in patients of the inactive phase. The mean OKT4+/OKT8+ ratio was not significantly different from that of the controls; however, values of the OKT4+/OKT8+ ratio were abnormal in some patients, and there were more cases with lower ratio values in the active than in the inactive patients. | |
| 3535311 | [Immunoreactive diseases in pregnancy]. | 1986 | Immunoreactive diseases in pregnancy are not frequent and it is important to guarantee an optimal and interdisciplinary treatment. The herpes gestationis is a pregnancy-specific disease of the skin with unknown origin and a good prognosis for mother and child. The progressional lupus erythematodes visceralis has a high risk for mother and child, but the rheumatoid arthritis shows remissions during pregnancy. The Basedow's disease and the autoimmune thyroiditis are needed a pregnancy-associated therapy to prevent a hyperthyreotic syndrome of newborns. The autoimmune haemolytic anemia and the thrombocytopenia have a high fetal risk although by intensive management. Myasthenia gravis may cause a transient neonatal syndrome. | |
| 2075373 | Stimulation of rheumatoid synovial and blood T cells and lines by synovial fluid and inter | 1990 | Rheumatoid arthritis (RA) is characterized by the presence of interleukin-2 (Il-2) receptor-positive T cells in the peripheral blood and synovial compartments. Utilizing the limiting dilution technique, the precursor frequencies of Il-2 responsive T cells were determined in peripheral blood and synovial sites from RA patients and in the blood of normal donors. The frequencies of Il-2 responsive T cells were significantly higher in RA patients (range from 1/180 to 1/7432) compared to normal donors (range from 1/400 to 1/8163). T-cell clones raised by the addition of Il-2 alone were predominantly of the CD4-positive phenotype. Peripheral blood T cells, synovial T-cell clones and lines derived from RA patients were co-stimulated with Il-2 and synovial fluid or supernatants from cultured synovial lining cells. This co-stimulation induced a strikingly enhanced proliferative T-cell response while synovial fluid alone was without effect. This stimulatory activity was found in the high molecular weight range (approximately 150 kDa) and could not be attributed to the action of immunoglobulins or known cytokines such as Il-2 or interleukin-1 (Il-1), suggesting the activity of a material that modulates the Il-2-dependent growth of T cells. The co-stimulatory capacity of synovial fluid with Il-2 may be relevant to the activated state, especially of synovial T cells. | |
| 1958562 | Sex steroids, glucocorticoids, stress and autoimmunity. | 1991 | Interest in the field of neuroimmunoendocrinology is in full expansion. With regard to this, steroid influence on the immune system, in particular sex steroids and glucocorticoids, has been known for a long time. Sex steroids are part of the mechanism underlying the immune sexual dimorphism, as particularly emphasized in autoimmune diseases. Immunosuppressive and anti-inflammatory effects of glucocorticoids are now considered a physiological negative feedback loop to cytokines produced during an immune and/or inflammatory response. Psychosocial factors may play a role in the development of immunologically-mediated diseases, e.g. autoimmune diseases. The nonobese diabetic (NOD) mouse, that develops an immunologically-mediated insulin-dependent diabetes mellitus (IDDM) is an interesting model to study the role of endogenous steroids. Insulitis is present in both sexes, but diabetes has a strong preponderance in females. Hormonal alteration, such as castration, modulates the incidence of diabetes, whereas environmental factors, such as stress, accelerate the disease. In the present paper, we have reviewed the role of gender, sex steroid hormones, stress and glucocorticoids in autoimmunity as well as analyzed their different levels of actions and interrelationships, focusing particular attention on the immunologically-mediated IDDM of the NOD mouse. | |
| 2025952 | Terminal complement complexes and C1/C1 inhibitor complexes in rheumatoid arthritis and ot | 1991 May | Terminal complement complex (TCC) and C1r-C1s-C1 inhibitor complex (C1/C1 INH) concentrations were measured in plasma and synovial fluid from patients with arthritis and related to other measures of disease activity. Both TCC and C1/C1 INH concentrations were significantly increased in patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis (plasma and synovial fluid, P less than 0.05) and normal subjects (plasma only, P less than 0.001). In the patients with RA, there was no correlation between plasma or synovial fluid TCC concentrations and IgM rheumatoid factor, immune complex or C1/C1 INH levels. However, in 10 patients with seronegative RA, C1/C1 INH and immune complex levels correlated significantly in synovial fluid (r = 0.69, P less than 0.05) although not in plasma (r = 0.52). Plasma and synovial fluid TCC and C1/C1 INH concentrations did not differ in rheumatoid patients with severe compared with mild joint disease (categorized by the Ritchie score). These results confirm a role for complement activation in RA but suggest that several mechanisms are involved in its pathogenesis. | |
| 3389109 | The role of type II collagen autoimmunity in otosclerosis revisited. | 1988 Mar | A recent theory, suggesting that otosclerosis results from autoreactivity to type II collagen present in the fetal cartilaginous remnants of the human bony labyrinth, is based on two observations. Otosclerotic patients have increased concentrations of circulating antibody to type II collagen, and immunization of rodents with cartilage collagen induces 'otosclerosis-like' lesions. Independent researchers have been unable to confirm the first promising results. No significant abnormalities could be found in immunized animals. We report the result of type II collagen antibody recordings in a well described group of otosclerotic patients and controls, and the histological findings in temporal bones of MRL/1-mice with spontaneous type II collagen autoreactivity. Our results cannot support the view of autoreactivity to type II collagen as an etiopathogenetic factor in otosclerosis. | |
| 3589456 | [Erythrocyte sedimentation rate and serum immunoglobulins in rheumatic pelvispondylitis]. | 1987 Mar | Blood sedimentation rate and balanced titration of immunoglobulins were studied in 59 patients presenting a ankylosing pelvispondylitis: in 30 of them, these examinations were repeated at an interval of 3-6 months. The sedimentation rate (Sed. rate) and the level of immunoglobulins G and A increased in the course of the disease, but an elective increase of the level of immunoglobulins A was not demonstrated. Neither the Sed. rate, nor the level of IgA are correlated to evolution criteria of the disease; a positive correlation is only found with the platelets number, in a vertical study of 59 patients. Nevertheless, the variations of the immunoglobulins A is positively correlated with alterations of the clinical condition as demonstrated in the longitudinal study carried out in 30 patients. This finding supports physiopathological hypothesis which incriminates microbial intestinal infections at the origin of evolutive bouts of ankylosing pelvispondylitis. | |
| 1898961 | Modulation of monocyte chemotactic function in inflammatory lesions. Role of inflammatory | 1991 Jan 15 | Monocyte recruitment and accumulation in the synovial tissue is pivotal in the evolution of rheumatoid arthritis (RA). In the present study we examined the chemotactic potential of monocytes obtained from synovial fluid (SF) of patients with RA. Functionally, SF monocytes exhibited greatly diminished chemotactic activity to C5a compared with monocytes from the peripheral blood. In contrast, their chemotactic responsiveness to the synthetic peptide, FMLP, was nearly normal. To define a mechanism for this differential chemotactic dysfunction, cell-surface receptors for C5a (C5aR) and FMLP (FMLP-R) were evaluated. Whereas FMLP-R expression was similar on both blood and inflammatory monocytes, C5aR expression was markedly reduced on SF cells. Because decreased C5a binding in certain RA SF samples could not be attributed to free C5a, known or suspected components of inflammatory SF were evaluated for their ability to modulate chemotactic ligand receptors. Bacterial products including LPS and streptococcal cell walls, which are potent monocyte activators, down-regulated C5aR without affecting FMLP-R. Moreover, the cytokines IFN-gamma and granulocyte-macrophage-CSF selectively decreased C5aR in parallel with decreased in vitro chemotactic activity to C5a. Thus, these data indicate that 1) synovial effusions may contain C5a and/or inflammatory mediators that modulate phenotypic and functional changes in monocytes, 2) chemotactic ligand receptors are independently regulated in inflammatory lesions, and 3) decreased C5aR expression and chemotactic potential likely provide a mechanism whereby monocyte-macrophages persist within the inflamed synovium. | |
| 2511620 | Mitogen-induced interleukin 2 and gamma interferon production by CD4+ and CD8+ cells of pa | 1989 Nov | The purpose of this study was to investigate interleukin 2 (IL-2) and gamma interferon (IFN-gamma) production by purified CD4+ and CD8+ cells isolated from peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and other inflammatory arthritides (non-RA). CD4+ and CD8+ cells were selected positively by immunomagnetic separation. Supernatants of unstimulated CD4+ and CD8+ cells from both compartments did not contain any detectable IL-2 or IFN-gamma, while supernatants of CD4+ and CD8+ cells stimulated with phytohaemagglutinin and irradiated Raji cells mostly contained both cytokines. In vitro stimulated SF CD4+ cells gave supernatants with significantly less IL-2 than supernatants from PB CD4+ cells, while in vitro stimulated SF CD4+-cell supernatants contained significantly more IFN-gamma. SF CD4+-cell supernatants contained significantly more IL-2 than the parallel CD8+ supernatants, while there was no significant difference with regard to IFN-gamma content. The pattern of differences between SF- and PB-derived T cells was the same for the two groups of patients, but the SF CD4+ cells from RA patients produced significantly less IL-2 than the corresponding cells from the non-RA group. The difference between SF and PB T cells with regard to lymphokine production is probably related to various degrees of in vivo pre-activation. The results do not indicate a major T-cell deficiency in relation to lymphokine production in RA. | |
| 3944161 | Conventional versus resurfacing total hip arthroplasty. A long-term prospective study of c | 1986 Feb | Fifty patients requiring bilateral total hip arthroplasty underwent a concomitant conventional hip arthroplasty on one side and an articular resurfacing procedure on the other, done by the senior one of us (M. A. R.). The average age of the patients was sixty-two years (range, twenty-one to eighty-seven years), and forty-seven of them were followed with serial radiographs and clinical evaluation for one year or more. The length of follow-up was five years for thirty-four patients with both prostheses intact. The average pain score for all hips at three years postoperatively was 5.5 points. Although the majority of patients at each follow-up interval did not prefer one procedure to the other, the conventional arthroplasty was significantly superior for those who had a preference, and radiographic evaluation revealed a statistically significant increased incidence of acetabular lucency at the bone-cement interface of the resurfacing arthroplasty at one, two, three, five, and seven years postoperatively (p less than 0.002). Two of the conventional prostheses were revised during this time-period (one because of infection and one, a broken stem) whereas thirteen (26 per cent) of the resurfacing prostheses were revised (eight hips had femoral loosening, five with concomitant acetabular loosening; three had acetabular loosening; and one had a femoral neck fracture) at an average of fifty-two months postoperatively (p less than 0.001). | |
| 2525986 | A global safety evaluation of etodolac. | 1989 Mar | Etodolac has previously been reported to have an excellent safety profile. Results of recent clinical trials and of a clinical practice study were compared with the previously reported safety data for etodolac. The total incidence of patient complaints and of laboratory abnormalities continues to be low, with no apparent increase in side effects with increasing patient age. In the clinical practice study, 60% of study events occurred early in therapy (before 10 weeks). These data support an excellent safety profile for etodolac. | |
| 3543119 | T15 group A streptococcal Fc receptor binds to the same location on IgG as staphylococcal | 1987 Feb 1 | Previous work has shown that IgG rheumatoid factors (RF) bind to the C gamma 2-C gamma 3 interface region of human IgG in the same area that binds staphylococcal protein A (SPA). Group A, C, and G strains of Streptococci possess Fc receptors that bind to IgG but not to fragments containing only the C gamma 2 or C gamma 3 domains. This work describes the binding site location on human IgG for the binding of the isolated Fc receptor from the T15 strain of a Group A streptococcus and its relationship to the site that binds SPA and the IgG RF. The isolated T15 Fc receptor (T15) with a molecular mass of 29.5 kD inhibited the binding of IgG RF to IgG. The binding of T15 itself to IgG was strongly inhibited by SPA (42.0 kD) and its monovalent fragment D (7 kD). Human IgG fragments consisting of the C gamma 3 domains did not inhibit the binding of T15 to IgG, whereas those with both domains were effective inhibitors. T15 did not bind to rabbit IgG fragments consisting of either the C gamma 2 or C gamma 3 domains, but did bind to those with both domains. An IgG3 myeloma protein was a poor inhibitor and has been shown to bind poorly to the IgG RF. Most IgG3 myeloma proteins did not bind to SPA. The substitution of Arg and Phe for His 435 and Tyr 436 is responsible for the poor binding of IgG3 to SPA and to the IgG RF. Chemical modification of His or Tyr on IgG reduced its ability to inhibit the binding of T15 to IgG. Reversal of the chemical modifications with hydroxylamine resulted in near complete restoration of inhibitory capacity. This information, collectively, coupled with the known positions in space of the His and Tyr residues in the C gamma 2-C gamma 3 interface region, verified that both His 435 and Tyr 436, and possibly His 310 and 433, are involved. These residues are also involved in binding SPA and the IgG RF. These data therefore indicate that the T15 Group A Streptococcal Fc receptor binds to the same location on the Fc of IgG as SPA and the IgG RF. The biologic relevance of these similarities between bacterial cell wall Fc receptors and IgG RF are not yet apparent, but suggest that RF could bear the internal image of these bacterial structures. | |
| 3132218 | Natural course of penicillamine nephropathy: a long term study of 33 patients. | 1988 Apr 16 | To elucidate the natural course of the nephropathy associated with penicillamine and thereby facilitate its clinical management 33 patients with rheumatoid arthritis who developed proteinuria during treatment with oral penicillamine were studied in detail throughout their renal illness. Renal biopsies were performed, and creatinine clearance and proteinuria were measured serially for 74 months (range 16-148 months). Fourteen patients developed proteinuria within six months after the start of treatment and 27 within 12 months. When treatment was stopped the proteinuria reached a median peak of 4.2 g/24 h (range 0.3-15.0 g/24 h) at one month (range 0-7 months) before resolving spontaneously by six months (12 patients), 12 months (21), or 18 months (29). In all patients but one, who developed carcinoma of the renal pelvis, proteinuria resolved by 21 months and its median duration was eight months. The median first and last measurements of creatinine clearance showed no appreciable change (80 ml/min and 78 ml/min), and no patient died from or needed treatment for renal failure. The HLA-B8 or HLA-DR3 alloantigen, or both, were identified in 10 patients. Renal biopsy specimens showed membranous glomerulonephritis in 29 patients, minimal change nephropathy in two, and electron dense deposits in the mesangial regions in two. In all the patients whose nephropathy was due solely to treatment with penicillamine the proteinuria resolved completely when the drug was withdrawn; renal function did not deteriorate, and corticosteroids were unnecessary. |