Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 2845745 | Chloroquine interaction with inflammatory human polymorphonuclear leucocytes. | 1988 Jul | The molecular in vitro association of radiolabelled chloroquine (CQ) with both normal resting and inflammatory polymorphonuclear leucocytes (PMNs) was measured. For this purpose a suitable ligand-association assay was developed to measure the cell association and the intracellular concentration of CQ. Under the influence of inflammatory stimuli PMNs display altered interaction with CQ. The intracellular concentration of CQ is reduced with 30 to 40% under inflammatory (disease) states when compared with non-inflammatory conditions. The mechanisms of CQ-PMN interaction associated with these altered intracellular concentrations of CQ are considered, with particular attention to the effects of rheumatic disease. Association experiments of CQ with PMNs performed in the presence of different established transport inhibitors showed that both diffusive uptake and carrier-mediated transport are involved in the cell accumulation of CQ in inflammatory PMNs. From these results, emphasis is given to three explanations for the decrease of the intracellular CQ concentration in inflamed PMNs. a) the expansion of the PMN volume under inflammatory conditions; b) the cytoplasmic or lysosomal pH changes and activation of the PMN Na+/H+ antiport by inflammatory stimuli; and c) the exocytic release of the granules (degranulation). Our data suggest that all these mechanisms, based on the events involved in inflammatory responses, may be involved in the decrease of the intracellular CQ concentration in inflammatory PMNs. | |
| 2512262 | Effect of the late complement components C5b-9 and of platelet-derived growth factor on th | 1989 | We examined the prostaglandin E (PGE) synthesis of cultured adherent synovial fibroblast-like cells (SFC) from patients with osteoarthritis (OA) in the noninflammatory state as well as with rheumatoid arthritis (RA). In cells from RA patients the spontaneous PGE release was generally higher compared to that of OA patients, but decreased fast with time in culture. After cell passage, similar PGE baseline levels were seen in cells of the two patient groups. The cells could then be stimulated by the terminal complement components C5b-9 or C5b-8. PGE synthesis was also stimulated by the platelet-derived growth factor (PDGF), interleukin-1 (IL-1), or lipopolysaccharide (LPS). The amount of PGE synthesis after incubation with PDGF, LPS and IL-1 was comparable to that released after C5b-9. Thus, like other inflammatory mediators C5b-9 and PDGF trigger the increased PGE production by SFC and thus may participate in the development of synovial inflammation and contribute to the pathogenesis of RA. | |
| 3162216 | Inactivation of tissue inhibitor of metalloproteinases by neutrophil elastase and other se | 1988 Feb 29 | Tissue inhibitor of metalloproteinases (TIMP) from cultured bovine dental pulp inhibits human rheumatoid synovial matrix metalloproteinase 3 (MMP-3) with a stoichiometry of 1:1 on a molar basis. Among the serine proteinases examined, human neutrophil elastase, trypsin and alpha-chymotrypsin destroyed the inhibitory activity of TIMP against MMP-3 by degrading the inhibitor molecule into small fragments. In contrast, the inhibitory activity of TIMP was not significantly reduced by the actions of cathepsin G, pancreatic elastase and plasmin. These data indicate that neutrophils which infiltrate tissues in various inflammatory conditions may play an important role in regulating TIMP activity in vivo through the action of neutrophil elastase. | |
| 1784883 | Demonstration of lymphatics in human synovial tissue. | 1991 | Using a cocktail of monoclonal antibodies PAL-E and DE-U-10 (anti-desmin), combined in double labelling techniques with the lectin Ulex europaeus agglutinin I (UEAI), vessels consistent with lymphatics were demonstrated in normal human synovial tissue. These vessels were negative for the monoclonal cocktail and positive for UEAI, were thin-walled and were located close to deep arterioles and venules as expected. Elastin was not found to assist identification of lymphatics in synovium. In rheumatoid arthritic synovium no vessels staining in the manner of normal lymphatics were found. This may indicate absence or change of phenotype of this type of endothelium in disease. | |
| 3042080 | Ileocolonoscopic findings in seronegative spondylarthropathies. | 1988 | Ileocolonoscopy with biopsy of caecum, ileocaecal valve and terminal ileum were performed on 232 patients with seronegative spondylarthropathies and on 65 control patients. Inflammatory gut lesions were found in 65% of the patients with reactive arthritis (ReA) and in 57% of the patients with ankylosing spondylitis (AS), especially in those with peripheral arthritis. The controls had a normal gut. This finding would suggest that exogenous factors causing inflammation of the gut lead to a disturbed permeability of the gut wall or to a deficient local immunological defence mechanism permitting antigens to enter the circulation, inducing the joint and tendon inflammation. Support for this hypothesis was provided by the results of a repeat ileocolonoscopy, disclosing a strong association between the presence of gut inflammation on biopsy and the persistence of joint inflammation. Patients presenting some of the histological lesions found on biopsy (especially active chronic lesions) and patients with proven Crohn's disease were found to share a genetic marker (HLA-BW62). This would suggest that some of the patients with seronegative spondylarthropathies suffer from a subclinical form of Crohn's disease of which the joint symptoms are the unique clinical manifestation. | |
| 1777559 | Class II major histocompatibility complex antigen expression on unstimulated and gamma-int | 1991 | HLA-DR, HLA-DQ, and HLA-DP antigen expression was assessed by immunofluorescent flow cytometry on monocytes from 19 patients with active multiple sclerosis (MS), 19 with inactive MS, 7 patients with early active rheumatoid arthritis (RA), and 19 normal controls. Percentage positivity and median channel fluorescence (MCF) were determined after separation of the monocytes (TO) and following 48 h culture with (T48 + IFN) and without (T48) recombinant gamma interferon (rIFN-gamma). The percentage positivity of the cells was normal at TO for all groups of patients for each of the HLA types but statistically significantly increased above normal, on monocytes from patients with inactive MS, after culture with rIFN-gamma. At TO, the MCF values for HLA-DQ, and HLA-DP were statistically significantly increased above normal on monocytes from patients with active MS indicating some pre-programming of the cells in vivo. After culture, when the carry-over from baseline TO values was eliminated, the increment in MCF for HLA-DR, on monocytes from patients with inactive MS, was statistically significantly lower than normal in the non-gamma-IFN cultures but was normal in the presence of rIFN-gamma. Conversely, the increment in MCF for HLA-DP on monocytes from patients with active MS was significantly lower than normal after culture with rIFN-gamma. Therefore, the stimulation required to increase antigen density on cells already expressing antigen may be different to that required to stimulate de novo expression on negative cells. Both systems appear to be abnormal in MS, possibly reflecting differences in disease activity, while only one system appears abnormal in RA. | |
| 3224444 | Anti-cardiolipin antibodies in ischaemic heart disease. | 1988 Nov | IgG and IgM anti-cardiolipin antibodies (ACA) were assayed by an ELISA technique in 86 patients with ischaemic heart disease (IHD) and compared to 124 healthy controls and to 62 patients with rheumatoid arthritis (RA) and 20 with tuberculosis (TB). IgG ACA levels in IHD, RA and TB were comparable and significantly higher than in controls (P less than 0.0001). IgM ACA was significantly higher in IHD and RA than controls (P less than 0.0001) but not TB (P = 0.045). The number of IHD patients with raised ACA (IgG and/or IgM) was significantly greater than in RA or TB. (chi 2 = 30.77, P less than 0.0001). ACA were raised in 80.2% IHD patients on one or more occasions during a 1-11 day (mean 4.7) hospital admission. There was no difference in either ACA levels or in the frequency of ACA elevation in patients with stable or unstable angina pectoris or myocardial infarction. We conclude that there is a strong association between IHD and ACA with potentially important therapeutic implications. | |
| 2525982 | A review of the antiarthritic efficacy and safety of etodolac. | 1989 Mar | Etodolac (Lodine, Ramodar, Ultradol), an anti-inflammatory, analgesic agent, is the first of a new class of nonsteroidal anti-inflammatory drugs (NSAIDs), the pyranocarboxylic acids. A review of the literature on numerous clinical studies showed that etodolac (200 to 600 mg/day) is effective in the treatment of osteoarthritis and rheumatoid arthritis. Etodolac has also been shown to be very well tolerated. In double-blind studies, there were no significant differences in the incidences of new patient complaints except for indigestion between etodolac-treated groups and placebo-treated groups. Gastrointestinal microbleeding associated with etodolac was comparable to that with placebo and was significantly less than that associated with other commonly used NSAIDs, such as ibuprofen, indomethacin, piroxicam, and naproxen. The results of laboratory tests, including a detailed analysis of hepatic and renal function, have revealed few abnormalities, most of which were clinically unimportant. When administered to healthy subjects, etodolac had no pharmacokinetic interactions with three other drugs that are highly bound to serum protein: warfarin, glyburide, and phenytoin. | |
| 2623661 | IL-2 enhancing factor(s) in B cell supernatants from patients with rheumatoid arthritis or | 1989 Nov | Culture supernatants of B cells from patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) in the active stage enhanced interleukin 2 (IL-2) dependent proliferation of CTLL A/J cells. This activity, designated B cell-derived growth-enhancing factor-2 (BGEF-2), was recovered by gel filtration of a molecular weight between 15,000 and 20,000. BGEF-2 itself did not show IL-2 activity nor IL-1 activity, and BGEF-2 activity was not detected in the following cytokines: Interferon-alpha (IFN-alpha), interferon-gamma (IFN-gamma), tumor necrosis factor (TNF), interleukin 4 (IL-4), interleukin 5 (IL-5) and interleukin 6 (IL-6). Furthermore, BGEF-2 was distinguishable from B cell-derived growth-enhancing factor described in a previous paper [Kang et al. (1987) J. Immunol., 139, 1154-1160]. BGEF-2 was produced by B cells from patients with RA or SLE only when the patients were in the active stage. BGEF-2 enhanced IL-2-dependent growth of peripheral blood T cells from patients with active RA, but did not enhance the growth of T cells from healthy volunteers. These results suggest that BGEF-2 is a B cell-derived lymphokine which plays an important role in the pathogenesis of RA and SLE. | |
| 3772930 | Coexistence of rheumatoid nodulosis and gout. | 1986 Aug | The case of a 42-year-old white male with a 7-year history of multiple subcutaneous nodules and intermittent episodes of acute arthritis is presented. The patient was found to have monosodium urate crystals on joint aspiration and rheumatoid nodules on biopsy. Our patient, the first reported case of coexistent rheumatoid nodulosis and gout, emphasizes the importance of a thorough evaluation and the need to account for all available clinical and laboratory data. The classification system, differential diagnosis and clinical manifestations of patients presenting with rheumatoid nodules are briefly reviewed. | |
| 3310942 | Cimetidine therapy in nonsteroidal anti-inflammatory drug gastropathy. Double-blind long-t | 1987 Oct | To assess the efficacy of cimetidine in treating and preventing gastric mucosal lesions associated with nonsteroidal anti-inflammatory drug (NSAID) therapy (NSAID gastropathy), we endoscopically studied 104 patients taking NSAIDs for a variety of rheumatic diseases. Fifty-six percent (22/43) of patients randomized to cimetidine 300 mg four times a day and 52% (22/42) of those randomized to placebo showed progression of endoscopic lesions during the eight-week short-term phase. Thirty-nine patients whose endoscopic lesions improved were then randomized to a ten-month maintenance regimen of either cimetidine 400 mg at bedtime or placebo. Fifty percent (7/14) of placebo-treated and 42% (5/12) of cimetidine-treated patients showed progression of lesions during the maintenance phase. The failure of cimetidine to offer any significant benefit under these protocol conditions reflects the fundamental difference in pathophysiologic features between classic acid-mediated ulcer disease and NSAID gastropathy. | |
| 1667942 | Interleukin 1 and tumor necrosis factor-alpha synergistically increase the production of i | 1991 Mar | We have previously reported that synovial cells could participate in B cell differentiation processes in rheumatoid arthritis (RA) by producing interleukin-6 (IL-6) spontaneously or in response to interleukin-1 (IL-1) stimulation. In this paper, we examined the effects of tumor necrosis factor-alpha (TNF-alpha) on IL-6 production by human synovial fibroblasts. TNF-alpha, as well as IL-1, is a putative relevant molecule in the inflammatory process and in articular destruction in RA. Both IL-1 and TNF-alpha induced IL-6 production by synovial fibroblasts in a dose dependent manner. When synovial fibroblasts were stimulated by IL-1 and TNF-alpha in combination, IL-6 production increased synergistically after 48 hr of a 72 hr culture period. Kinetic studies revealed that the presence of both cytokines at the early phase of stimulation was required for the synergistic effect. These results suggest that TNF-alpha could be involved in a cytokine network in the affected joints of RA and could contribute synergistically with IL-1 to the IL-6 production by synovial fibroblasts in vivo. | |
| 2373514 | Mechanism of action of an inhibitor of complement-mediated prevention of immune precipitat | 1990 Jun | Glycoprotein 60 (gp60) is a normal plasma protein (mean concentration in normal serum 34 micrograms/ml) that is present in increased levels (mean concentration 97 micrograms/ml) in the sera of patients with rheumatoid arthritis (RA). Purified gp60 binds to IgG but not to IgM, and competitively inhibits the binding of C1q. In fluid-phase studies, purified gp60 was shown to reduce immune complex-mediated complement activation in a dose-dependent manner. The addition of Fab anti-gp60 to normal serum was associated with (i) increased levels of complement-mediated prevention of immune precipitation (PIP); (ii) increased total haemolytic complement activity when EAIgG, but not when EAIgM, were used as targets; and (iii) increased immune complex-mediated complement activation. Thus gp60 appears to regulate immune complex-mediated classical pathway activation. The findings that Fab anti-gp60 (i) only partly restored PIP in RA sera showing reduced PIP levels and (ii) only partly reduced inhibition of PIP by RA sera, show that gp60 is not entirely responsible for these abnormalities. | |
| 2189302 | Outcome of first-trimester exposure to low-dose methotrexate in eight patients with rheuma | 1990 Jun | PURPOSE: Methotrexate (MTX), when used to treat malignancy or psoriasis, has been implicated in anecdotal reports as a teratogen or abortifacient in the first trimester of pregnancy. We are unaware of any previous reports that describe the course of gestation and the effect on subsequent offspring in patients treated with low-dose oral MTX for rheumatoid arthritis, and therefore present our experience. PATIENTS AND METHODS: We report on eight women experiencing 10 pregnancies. Mean number of weeks of gestation while taking MTX was 7.5 (range 2 to 20 weeks). Outcome of pregnancies included five full-term babies (FTB), three spontaneous abortions (SAB), and two elective abortions. RESULTS: There were no significant differences in either the FTB or SAB group when considering risk factors including smoking, alcohol, concomitant medications, and age. One of three in the SAB group had recurrent abortions prior to MTX therapy. All five of the FTB group had uncomplicated pregnancies and deliveries. All offspring were of normal height and weight at birth with no physical abnormalities. All children reached growth, development, and intellectual stages normally, and their present mean age is 11.5 years. No observed learning disabilities or medical abnormalities have occurred in any of these children. CONCLUSION: In this uncontrolled study we failed to demonstrate tertogenicity of MTX. However, the possibility of abortion due to MTX use remains. | |
| 2472921 | Ba and Bb fragments of factor B activation: fragment production, biological activities, ne | 1989 | Factor B is a centrally important component of the alternative complement pathway. Alternative pathway activation results in factor B cleavage and production of the amino-terminal Ba and the carboxyl-terminal Bb fragments which have molecular weights of approximately 30,000 and 63,000 daltons, respectively. Both Ba and Bb fragments have been reported to express a variety of biological activities in vitro. Thus, binding of Ba and Bb fragments to specific B lymphocyte surface receptors modulates proliferation of prestimulated B cells. In addition, the enzymatically active Bb fragment induces activation and spreading of human and murine macrophages and monocytes as well as regulates C5a des Arg chemotactic activity. The fractional catabolic rate and metabolism of factor B in vivo is similar to that of C3, C4 and C5 complement proteins, which are among the most metabolically active plasma proteins in the circulatory system. Factor B hyperconsumption and increased catabolism, concomitant with factor B fragment production, occurs in a wide variety of diseases, including gram-negative sepsis, autoimmune diseases and burns. Measurement of alternative pathway activation in vivo has been attempted utilized a number of different techniques to quantitate factor B fragments in biological fluids. However, the recent development of enzyme immunoassays (EIA) employing monoclonal antibodies (MoAbs) reactive with factor B fragment neoepitopes provides the best approach currently available for the quantitation of factor B activation fragments. Results obtained using these new MoAb-based EIAs have indicated that factor B fragment concentrations were elevated, as compared with normal donor levels, in EDTA plasma samples obtained from patients with rheumatoid arthritis and systemic lupus erythematosus (SLE). Plasma concentrations of factor B fragments, especially Ba fragment levels, in these patients showed a positive correlation with disease activity scores. One of the highest disease activity correlations was obtained with Ba fragment measurements in SLE plasma samples. In fact, the results strongly suggested that quantitation of Ba fragment levels in SLE plasma samples more accurately reflected disease activity and was a more sensitive predictor of impending flare in these patients than any other test(s) currently available. | |
| 1947297 | Magnetic resonance imaging of the knee. | 1991 Aug | Magnetic resonance imaging of the knee was the first successful application of this technique to the articular system. The advantages of magnetic resonance imaging over arthrography include its noninvasive nature, the ability to evaluate the knee in multiple planes without patient repositioning, the absence of ionizing radiation, the capacity to evaluate the joint even in the presence of joint effusion, and the ability to examine the inner structure of the meniscus as well as its surface. Although magnetic resonance imaging initially was used to study the menisci and cruciate ligaments, the technique has been expanded to include the evaluation of various conditions and all the structures of the knee joint and surrounding soft tissues. | |
| 3104587 | Sex hormone status in women suffering from rheumatoid arthritis. | 1986 Dec | We studied the sex hormone status of 21 seropositive (IgM-RF) women with rheumatoid arthritis (RA), who were subdivided according to their premenopausal and postmenopausal status. Age matched women with secondary osteoarthritis were used as controls. The hormones evaluated were luteinizing hormone (LH), follicle stimulating hormone (FSH), prolactin (PRL), 17-beta-estradiol (E2), progesterone (Pg), testosterone (T), delta 4-androstenedione (A), dehydrotestosterone (DHT), dehydroepiandrosterone sulphate (DHEAS) and cortisol (C). Normal concentrations of all the hormones considered were found in premenopausal women with RA. Statistically higher concentrations of T (p less than 0.05), A (p less than 0.05) and DHEAS (p less than 0.01) were observed in postmenopausal women with RA when compared to controls, whereas no differences were found for all other hormones studied. Although the significance of observed relative hyperandrogenism in postmenopausal women with RA is not clear, our data seem to indicate that sex hormone levels are altered in patients with RA. | |
| 3383449 | A new assay uses monoclonal anti-Rh(D) antibodies to determine rheumatoid factor specifici | 1988 Mar | A new method has been developed to determine the specificities of polyclonal rheumatoid factors (naturally occurring antibodies which react with human Fc gamma) (RF) found in sera from patients with rheumatoid arthritis. In this method, monoclonal anti-Rh(D) antibodies of known IgG isotype and allotype are bound to erythrocytes and then act as the target IgG antigen for RF in a direct haemagglutination test. Using two monoclonal anti-D antibodies of the IgG3 isotype and G3m(21) allotype, which were cloned from different donors, we found that a large number of rheumatoid sera reacted with both these G3m(21) proteins. In contrast reactivity of rheumatoid sera with polyclonal anti-D of the G3m(21) allotype in the direct haemagglutination test was rare. A strong correlation was found between reactivities to both G3m(21) monoclonal anti-D antibodies but not with a monoclonal anti-D antibody carrying the alternative allele, namely G3m(5). Haemagglutination inhibition experiments using human paraproteins of known IgG isotype and allotype provided some additional evidence that this method can detect RF with specificity for the G3m(21) allotypic determinant or a related allotypic determinant in polyclonal rheumatoid sera. When each patient's autoantibody response was related to their Gm phenotype, we found that the frequency of reactivity for G3m(21) monoclonal anti-D antibodies was significantly greater in patients negative for G3m(21) than in patients positive for the G3m(21) allotype. IgM preparations from patients' sera were dissociated at acid pH but no 'hidden' antibodies were found. We suggest trans-placental sensitization as one of several possible interpretations of this finding. | |
| 3006701 | Treatment of rheumatoid synovitis of the knee with intraarticular injection of dysprosium | 1986 Feb | One hundred eight knees of 93 patients with seropositive rheumatoid arthritis and persistent synovitis of the knee were treated with an intraarticular injection of 270 mCi of dysprosium 165 bound to ferric hydroxide macroaggregate. Leakage of radioactivity from the injected joint was minimal. Mean leakage to the venous blood 3 hours after injection was 0.11% of the injected dose; this corresponds to a mean whole body dose of 0.2 rads. Mean leakage to the liver 24 hours after injection was 0.64% of the injected dose; this corresponds to a mean liver dose of 3.2 rads. In 7 additional patients examined, there was negligible or near negligible activity found in the draining inguinal lymph nodes. One-year followup was possible for 74 knees (63 patients). Sixty-one percent of the knees had good results, 23% had fair results, and 16% had poor results. There was a direct correlation between the radiographic stage and response to treatment. In knees with stage I radiographic changes, 72% showed good results; 93% showed improvement. In knees with stage II changes, 59% showed good results; 81% showed improvement. These preliminary results indicate that dysprosium 165-ferric hydroxide macroaggregate is an effective agent for radiation synovectomy. The low leakage rates observed offer a definite advantage over agents previously used. | |
| 3704718 | Hepatotoxicity after long-term methotrexate therapy. | 1986 May | To reassess the need for repeat liver biopsies in patients receiving long-term methotrexate therapy, we reviewed the results of 15 biopsies in 14 such patients seen from 1979 to 1984 at the Medical University of South Carolina. Significant changes in liver histology were found in seven patients. These findings did not correlate with biochemical abnormalities, presence of anemia or obesity, or age when methotrexate therapy was initiated. Four of the 15 biopsies (27%) showed grade III or IV histologic changes (fibrosis or cirrhosis), which led to discontinuance of treatment. The single most significant factor predisposing to toxicity appeared to be the duration of therapy, though the cumulative doses, no patient with grade III or IV histology had been treated for less than five years. Thus, surveillance liver biopsies at suitable intervals are advisable once the patient has been treated for five years or more. Conversely, liver biopsies within the first five years of treatment with methotrexate appear not to be necessary, though these results should be confirmed in a larger patient group. |