Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rheumatoid arthritis (RA) is a chronic idiopathic disease characterized by persistent inflammation of the synovium, local destruction of bone and cartilage, and a variety of systemic manifestations. Although the etiologic stimulus has not been identified, rheumatoid synovitis is characterized by persistent immunologic activity, with CD4(+)/CD29(+) memory T cells prominently involved. Many of the local and systemic manifestations of RA appear to result from the production of a variety of cytokines within the inflamed synovium. A number of other inflammatory mediators produced in the rheumatoid synovium, including arachidonic acid metabolites, vasoactive amines, platelet-activating factor, and complement cleavage products contribute to the inflammatory process. In addition, the local production of immunoglobulin and the autoantibody, rheumatoid factor, along with the local production of immune complexes and complement activation, play a major role in the destructive potential of rheumatoid synovitis. The driving force behind rheumatoid inflammation, however, is likely to be CD4(+) T cells responding to an antigenic epitope in the synovium in an HLA-DR restricted manner. Understanding the immunopathogenic process underlying rheumatoid inflammation should provide insight into approaches to control the disease effectively and specifically.
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PMID:Cellular basis for rheumatoid inflammation. 200 81

Scleroderma (progressive systemic sclerosis [PSS]) is known to be associated with abnormal T cell immunoregulation. In the present study, we evaluated lymphocyte phenotypes in patients with PSS and normal control subjects by flow cytometry and monoclonal antibodies for total T (CD3), T suppressor (CD8), T helper (CD4), T helper-inducer (CDw29), T suppressor-inducer (CD45R), human leukocyte antigen, DR+B (CD19), DR+T, and natural killer subsets, HNK-1 (CD57) and NKH-1 (CD56) cells. Patients with PSS compared to normal subjects had significantly lower percentages of CD3+ (p less than 0.005) and CD8+ (p less than 0.05) (similar to several patients with rheumatoid arthritis also evaluated), as well as CD45R (p less than 0.05), T+DR+ (p less than 0.05), and NKH-1 (CD56) (p less than 0.0005) cells. Patients with PSS with late-limited or generalized disease had lower percentages of CD8+, CD19, NKH-1+, and CDw29, but higher percentages of CD4+, HNK-1, and CD45R cells compared to patients with early stage disease, but these results were not statistically significant. These unique alterations in patients with PSS may prove to be useful in monitoring the stage of disease activity for therapy and further define immunologic defects.
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PMID:Altered T cell subpopulations and lymphocytes expressing natural killer cell phenotypes in patients with progressive systemic sclerosis. 201 71

The development of human anti-mouse monoclonal antibodies (HAMAs) was investigated in 10 patients with rheumatoid arthritis (RA) who had undergone an experimental therapeutic trial with an anti-CD4 monoclonal antibody. In this patient group, the antibody 16H5 of the IgG1 isotype had been administered in a median total dosage of 140 mg per treatment cycle. Four patients took part in a second treatment regimen 6-8 weeks later. After the first treatment cycle, detectable HAMAs developed in 5 out of 10 patients. In 4 individuals undergoing a second course of therapy, increases of HAMAs were evident only in the 3 patients with previous HAMA responses. HAMAs were primarily of the IgG isotype, while the presence of rheumatoid factors usually interfered with the detectability of IgM HAMAs. However, using isolated F(ab)2 fragments of the monoclonal reagent used for therapy, HAMAs of the IgM isotype were also detectable. HAMAs of the IgG isotype did not exceed levels of 2.0 mg/liter after a single treatment cycle and 2.2 mg/liter after a repeated cycle. No IgE responses were detectable. Absorption experiments indicated that approximately 25% of the HAMA activity was directed against specific determinants of the 16H5 monoclonal antibody, presumably including anti-idiotypic reactivities. These data demonstrate that HAMAs developed only in a proportion of RA patients treated with the anti-CD4 monoclonal antibody 16H5. However, the amounts were rather low compared to other monoclonal reagents used in cancer patients and were therefore allowed for repeated applications without an apparent loss of efficacy.
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PMID:Human anti-mouse antibody response induced by anti-CD4 monoclonal antibody therapy in patients with rheumatoid arthritis. 201 13

Recent experimental and clinical data point to the T helper lymphocyte subset as playing a central role in the pathogenesis of rheumatoid arthritis (RA). Thus, a therapeutic strategy aimed specifically at the CD4 T cell subset is warranted. We treated patients with active RA for 7 days with a daily dose of 20 mg of CD4 monoclonal antibody M-T151, administered intravenously over 30 minutes. There were no negative side effects. According to changes in the combined parameters of Ritchie articular index, pain assessment, grip strength, and morning stiffness, 6 patients had a good response. Clinical improvement was greatest approximately 2 weeks after termination of the therapy and lasted from 4 weeks to 6 months. Of the serologic parameters of inflammation, only the C-reactive protein level improved in the patients with a favorable response. Close immunologic monitoring revealed a transient, selective depletion of CD4+ T cells after each infusion. During the entire treatment period, residual circulating CD4+ cells were found to be coated with CD4 antibody, whereas free antibody was detected in the serum only for approximately 8 hours after each infusion. Immediately after infusion, soluble CD4 antigen appeared in the serum. In addition to the cell-bound CD4 antibody, complement components could be detected on the surface of the remaining CD4+ cells. The proliferative response of peripheral blood mononuclear cells to purified protein derivative was significantly diminished 4 weeks after cessation of antibody treatment. Six patients showed a weak antibody response to mouse immunoglobulin. In 4 of the responders who received a second course of therapy (2 of them as outpatients), a therapeutic effect was noted that was similar to that after the first course. Only 1 patient, who had low titers of serum IgE anti-mouse Ig antibodies, showed a mild anaphylactic reaction at the end of the second course of therapy. Treatment of RA with the monoclonal CD4 antibody M-T151 seems to be a promising alternative, although the optimal dose and the regimen of administration are still to be defined.
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PMID:Treatment of rheumatoid arthritis with monoclonal CD4 antibody M-T151. Clinical results and immunopharmacologic effects in an open study, including repeated administration. 202 6

Peripheral blood mononuclear cells (PBMC) from patients with systemic sclerosis (SSc) produced increased amounts of interleukin-2 (IL-2), in a dose-dependent manner, in response to stimulation with human type I collagen, whereas PBMC from normal subjects did not. At a dose of 50 micrograms human type I collagen/10(6) PBMC, PBMC from SSc patients (n = 17) produced 8 times as much IL-2 as did PBMC from 16 normal subjects (P less than 0.005) and 3 times as much as did PBMC from a group of 13 rheumatoid arthritis patients (P less than 0.05). In contrast, IL-2 production by PBMC after nonspecific stimulation with the mitogen, phytohemagglutinin, did not differ among the SSc, rheumatoid arthritis, and normal control groups. Cell depletion experiments indicated that the IL-2-producing cells in SSc patients are CD4+. Thus, SSc patients have CD4 cells that are specifically sensitized to human type I collagen and can produce increased levels of IL-2. Measurement of IL-2 production stimulated by human type I collagen may be useful in evaluating disease activity, and further investigation of this process may contribute to the delineation of the pathogenesis of SSc.
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PMID:Increased interleukin-2 production in response to human type I collagen stimulation in patients with systemic sclerosis. 202 11

The drug treatment of progressive rheumatoid arthritis (RA) is discussed with emphasis on second line agents used both singly and in combination. NSAIDS play a supportive role in the management of RA. Low dose prednisolone is acceptably safe and effective in long term use whereas pulsed steroids and intra-articular use is reserved for short term control of disease. Antimalarials are rarely valuable as sole agents in progressive arthritis. The use of sulphasalazine, gold thiomalate, d-penicillamine, auranofin, methotrexate, azathioprine and cyclophosphamide in rheumatoid arthritis and their place in the therapeutic strategy are discussed. The reported use of combination chemotherapy has not shown the expected additive benefits although azathioprine, methotrexate and hydroxychloroquine combination may prove to be better than single agents. Recently cyclosporine and gamma interferon have not been shown to be highly efficacious. Of the new therapies monoclonal antibodies to CD4 and CD5 positive lymphocytes are showing promise of marked efficacy in the short term. Sustained control of synovitis appears to improve the long term outcome but better strategies and better drugs are needed.
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PMID:Drug treatment of progressive rheumatoid arthritis. 202 52

Changes in immune competent tissues of the HIV-1-infected person reflect to a certain extent the kind and intensity of immunological dysregulations. The diagnostic approach, however, must include immunophenotyping of cells, immunovirological studies of virus distribution in diseased tissues, and functional tests in addition to classical morphology. The latter technique alone just serves as a crude screening method since structural lesions in lymphoid tissues do not permit discrimination from other HIV-independent immune deficiency and autoimmune disorders. Although the overall appearance of lymph nodes in HIV infection and in chronic autoimmune disorders, such as collagen vascular diseases (e.g., rheumatoid arthritis and systemic lupus erythematosus), is similar, immunophenotyping shows a progressive loss of CD4 cells in HIV infection yet a quantitative increase in this cell population in autoimmune disorders (Krueger 1985a). In addition, there are other persistent active infections by lymphotropic viruses (e.g., EBV or HHV-6) which can cause structural and cellular changes in lymphoid tissues closely resembling HIV-induced lesions (Krueger et al. 1988b; Krueger 1985b). The pathological diagnosis therefore nedds to be supplemented by serological studies and--in selected cases--by in situ hybridization for the demonstration of viral genome. Southern blotting for viral DNA can only detect high numbers of viral genome copies in tissue extracts, not in which cell population the virus resides (e.g., malignant cells vs associated "normal" cells), while the polymerase chain amplification reaction, the most sensitive of all (Buchbinder et al. 1988), cannot yet differentiate between latent and (disease-related) active infection. Taking into consideration the above-described precautions in the evaluation of lymphatic lesions, there are a number of characteristic changes which reflect well the sequelae of HIV infection itself and of the ensuing immune dysregulation. Progressive loss of CD4 cells in the paracortex of lymph nodes and in the peripheral blood leads to inversion of the CD4/CD8 ratio. Loss of demonstrable CD4 cells is probably the consequence not only of cell lysis by HIV-1 infection (note: discrepancy between HIV-1 genome positive cell numbers and depletion of CD4 cells) but also of decreased CD4 marker synthesis in infected cells (Stevenson et al. 1987). In this context it is interesting that Fouchard et al. (1986) were able to show HIV expression in CD8 cells and theorized that these developed from infected CD4 cells which subsequently lost the CD4 epitope and expressed CD8.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Immunological dysregulation of lymph nodes in AIDS patients. 204 8

It is widely admitted that the non steroidal anti-inflammatory drugs (NSAID) inhibits the synthesis of prostaglandins by blocking the membrane cyclo-oxygenase. The anti-inflammatory activity of these molecules is partly explained by the vaso-dilatational action of PG2 in particular. However this effect alone cannot account for all the properties of NSAID. The latter have an inhibitory action at the level of the various functions of neurophil leucocytes and to a lesser degree at the level of macrophages. For immune system itself, it seems the NSAID have a rather immunostimulant effect due to a major action on T lymphocytes. In the course of rheumatoid arthritis (RA), the NSAID are unable to modify the ratio CD4/CD8. Yet they may decrease the production of the rheumatoid factor (RF). This ability is related to a loss of the normal suppressive T cells inhibition exerted by PG. Besides the NSAID seem unable to modify the natural killer function (NK). Finally, the impact on the synthesis of interleukins (IL) notably 1 and 2 does not seem clear. Indeed several research papers give us contradictory results between animals and men and between physiological or pathological situations.
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PMID:[Action of non-steroidal anti-inflammatory agents on the immune system]. 205 29

Monoclonal antibodies (mAb) to the CD4 surface molecule inhibit the function of CD4+ T cells in vitro and have been used for treatment of autoimmune diseases in several animal models. Recently, an anti-CD4 mAb has been described that improved the clinical situation of rheumatoid arthritis (RA) patients although no change in laboratory parameters could be observed. Here, we report on a different high-affinity anti-CD4 mAb (MAX.16H5) and its use for treatment of RA. Reduction of the Ritchie index, morning stiffness and the number of swollen joints demonstrated the clinical benefits of the therapy. In addition, laboratory parameters like ESR, CRP, and rheumatoid factor were reduced in 6/12 treatments. A rapid depletion of CD4+ T cells was observed in all patients which reached a minimum 1 hour after administration. However, efficacy of treatment did not correlate with T cell depletion. The antibody accumulates at the site of inflamed joints as detected by 99m-Tc-labelling. Affected digital joints were detected earlier by virtue of helper T cell imaging than by conventional bone scans.
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PMID:An anti-CD4 antibody for treatment of chronic inflammatory arthritis. 206 85

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.
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PMID:Stimulation of rheumatoid synovial and blood T cells and lines by synovial fluid and interleukin-2: characterization of clones and recognition of a co-stimulatory effect. 207 73


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