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)

High intravenous doses (400 mg/kg) of gammaglobulin (IVIG) were administered monthly for six months to 7 patients with severe rheumatoid arthritis (RA). In all cases, previous treatment with NSAIDs and corticosteroids and in 3 of them with gold and/or methotrexate had been ineffective. A 50 per cent improvement of Ritchie index was obtained in 6/7 patients, morning stiffness was reduced from greater than 2 hours to less than 30 minutes in 6/7 patients. Swollen joints and Lee index improved in all patients. ESR did not show any change but RCP improved in 6/7 patients. The study of lymphocyte subpopulation showed no substantial changes in CD20+, CD3+, CD4 and CD8 cells as well as in CD4/CD8 ratio and a significant increase in 2H4+T cells without changes in 4B4+ subpopulation. IVIG improved the clinical and laboratory features of patients with severe RA. The major problem raised by IVIG therapy is its high cost suggesting that this therapy should only be applied in well selected patients with RA.
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PMID:[High-dose immunoglobulins for the treatment of rheumatoid arthritis: pilot study of 7 cases]. 171 19

Monoclonal anti-CD4 antibodies have been introduced into the treatment of rheumatoid arthritis. A depletion of CD4+ T-cells down to 8% of the origin level (p less than 0.0001) followed the antibody application. Moreover, there was a significant reduction of blood monocytes to 30% (p less than 0.001). A reduced lymphocyte proliferation induced by antigens or mitogens was found in parallel. Prior to treatment, monocyte-macrophage activation in rheumatoid arthritis was signified by an increased expression of HLA-class II antigens and the CD14 antigen, and by an increased production of neopterin and interleukin-1. Anti-CD4 treatment resulted in a significant reduction of elevated levels of neopterin, beta 2-microglobulin in serum as well as IL-1 production in vitro.
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PMID:[Suppression of monocyte-macrophage activation by anti-CD4 therapy in patients with chronic polyarthritis]. 171 88

Ten patients with severe rheumatoid arthritis were treated with a murine monoclonal anti-CD4 (B-F5) antibody in an open study (one with 10 mg/day, 2 with 15 mg/day, 7 with 20 mg/day) for 10 consecutive days. Tolerance was excellent. All patients improved during treatment clinically (Ritchie's index, morning stiffness, pain scale) (p = 0.005), as well as biologically C-reactive protein (p = 0.008) with an average 60% reduction of each of these variables at Day 15, and clinical benefit lasted over 6 months in some patients. No significative depletion was noted in total lymphocyte or CD3, CD4, CD8, CD20, positive cells after treatment. Evidence of murine immunization was found in only 2 patients.
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PMID:Therapeutic use of monoclonal anti-CD4 antibody in rheumatoid arthritis. 171 69

Lymphoid cell phenotype was investigated in the peripheral blood, synovial fluid, and synovial tissue of sixteen patients with rheumatoid arthritis (RA). In the peripheral blood of RA patients the proportion of cells expressing HLA-DR and beta 2-microglobulin receptors was higher than in normal controls, whereas the proportion of cells that were CD5+ (i.e. were T lymphocytes) was lower. Expression of the other cell surface antigens studied remained in the normal range. In the synovial tissue and synovial fluid of RA patients there was an increased percentage of cells expressing HLA-DR, beta 2-microglobulin receptors, CD25, CD5, CD4, and Thy-1, but the proportion of CD8+ cells was significantly decreased compared with that seen in peripheral blood. The CD4+/CD8+ ratio in RA joints was therefore significantly higher than that in peripheral blood. The proportion of cells expressing HLA-DR correlated with disease activity.
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PMID:Local activation of lymphoid cells in rheumatoid synovium. 171 12

A phase I/II trial of the anti-CD4 monoclonal antibody (mAb) was undertaken in seven rheumatoid arthritis patients in order, (1) to investigate changes in clinical symptoms and possible side effects, and (2) to study the pharmacokinetics and to determine the dose required to achieve saturation of antibody binding sites on blood leucocytes. BL4mAb is a murine IgG2a which binds to the group 2B epitope of the V1 N terminal domain of the CD4 molecule. It inhibits syncitium formation by human immunodeficiency virus-infected cells. BL4 was administered by one hour-long intravenous infusion each day, for 10 days. Doses were steadily increased from 20 mg/d to 40 mg/d in the first three patients (group I) in an attempt to reach a serum antibody residual level sufficient to saturate CD4+ circulating cells. The three other patients (group II) received a dose of 40 mg/d during 10 consecutive days. One patient who presented chills and mild fever during the first BL4 infusion was not included in the analysis. No clinical side effects were observed in the six other BL4-treated patients. Clinical parameters of disease activity were improved within the first 14 days. Clinical improvement was still significant at day 30 in five patients, but at day 60, only the Ritchie index was still below pretreatment levels. Delayed type hypersensitivity reactions decreased in the three patients who exhibited positive reactions before BL4 administration. A transient drop in peripheral blood CD4+ lymphocyte counts occurred during each infusion in the first days of treatment. Pre-infusion CD4+ lymphocyte counts were moderately decreased within the first 8 days, but rose to pretreatment levels 3 days after the last infusion. BL4 residual levels in serum steadily increased to reach 8.0 micrograms/ml in group I and 9.8 micrograms/ml in group II. Saturation of BL4 binding sites was achieved after 2 days of treatment in all patients of group II but in only one of group I. Four out of six patients produced antibodies against the anti-CD4 mAb. Immunization appeared between days 12 and 50. This study shows that saturation of anti-CD4 mAb binding sites can be achieved by infusions of high doses (40 mg/d) of BL4 without clinical side effects. The results would encourage further placebo-controlled trials, since no definite conclusion can be drawn from the present study as regards clinical efficacy.
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PMID:Immunological effects of high dose administration of anti-CD4 antibody in rheumatoid arthritis patients. 177 12

In patients with systemic rheumatoid arthritis (RA) and extraarticular manifestation treated with plasma exchange or prednisolute-pulse-therapy, respectively, and followed by an additional immunosuppression by cyclophosphamide we have assessed the lymphocyte subpopulations of the peripheral blood and the cells expressing activating markers by means of monoclonal antibodies using fluorescence microscopy or fluorescence flow cytometry. Before therapy the patients showed a very different level of lymphocyte subpopulations tested. During treatment in both groups of patients there was not any uniform tendency in CD3, CD4 and CD8 positive cells. The percentage of activated lymphocytes was initially elevated and we found significant reduction, mainly in the 4th week after starting of therapy. Following in the most cases the level recovered to the state before therapy. For the single patients an individual pattern of reaction was evident in relation to the initial position before treatment.
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PMID:[Determination of lymphocyte subpopulations and their activation status in patients with rheumatoid arthritis treated with plasma exchange and pulse therapy]. 179 18

Immunization with native type II collagen (CII) of susceptible strains of mice (H-2q) induces a rheumatoid arthritis-like disease. Collagen-induced arthritis (CIA) is an experimental model for T cell-mediated autoimmune disease. To investigate the T cell receptor (TcR) repertoire involved in the pathogenesis of CIA, CII-primed DBA/1 mice were treated with various TcR V beta-specific monoclonal antibodies (mAb) using a protocol resulting in a long-term elimination of the target T cells. In vivo treatment with anti-CD4 mAb led to nearly complete protection against CIA. Mice injected with anti-V beta 8.1, 2 or anti-V beta 5.1, 2 mAb had a reduced incidence of arthritis (respectively 28.6% and 50% vs 84.6% for the control group). Administration of anti-V beta 2 mAb delayed the onset of the disease whereas injection of anti-V beta 6 or anti-V beta 11 mAb did not alter CIA. Moreover, the combined treatment with anti-V beta 2 and anti-V beta 5 mAb efficiently reduced the development of CIA. The humoral response to CII was down-regulated only in the groups of mice that were improved by the treatment. In vitro proliferative response to CII of lymph node cells from primed DBA/1 was partially blocked by addition of several anti-V beta mAb. Thus, our findings suggest that the overall T cell response to CII may be polyclonal while the T cell clones involved in the pathogenesis of CIA express a limited number of V beta chains.
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PMID:Therapy against murine collagen-induced arthritis with T cell receptor V beta-specific antibodies. 183 85

Ten patients (6 women and 4 men), with a group mean age of 65 years, defined as severe and with a mean follow-up period of 9 years and refractory to conventional treatments, were treated with monoclonal anti-CD4 antibodies in an open study. The monoclonal antibodies, of murine origin, were administered by intravenous route for ten consecutive days at a dose of 10 mg (1 patient), 15 mg (2 patients) or 20 mg (7 patients). Local and systemic tolerability were excellent. Clinical improvement was rapid (pain, morning stiffness, Ritchie index, p = 0.005 between D0 and D15), as was the paraclinical improvement (C-reacting protein, p = 0.008), although without achieving complete remission. The outcome revealed that the effect was more prolonged in patients treated with 20 mg per day than in the others, suggesting a dose-effect relationship. The improvement obtained may persist for more than 9 months in some patients. No significant change in immunological parameters was found at the end of the treatment (lymphocyte populations, immunoglobulins, complement). Only 2 out of 10 patients developed anti-mouse antibodies. As a result of its excellent tolerability and rapid effectiveness, this antibody appears to offer fresh therapeutic prospects in rheumatoid arthritis.
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PMID:[Therapeutic use of a monoclonal, anti-CD4 antibody in refractory rheumatoid polyarthritis. Preliminary results]. 187 15

T-gamma-lymphoproliferative disorder, a syndrome of T-cell lymphocytosis with neutropenia has been described in patients with various autoimmune disorders, especially rheumatoid arthritis. We report a case of T-gamma-lymphoproliferative disorder occurring in a 42-year-old white woman with a long history of dermatitis herpetiformis and subsequent development of Coomb's positive autoimmune hemolytic anemia and polymyositis. The peripheral blood lymphocytes showed the T-suppressor cell phenotype (CD2-, CD3-, CD8-, and CD4-). DNA analysis of the peripheral blood lymphocytes revealed a T-cell receptor beta-chain gene rearrangement and an immunoglobulin heavy-chain gene rearrangement. The patient's course was marked by numerous bouts of infection. The unique factor in this patient was the development of a plasma cell dyscrasia and amyloidosis prior to death.
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PMID:T-gamma-lymphoproliferative disorder arising in a background of autoimmune disease and terminating in plasma cell dyscrasia with primary amyloidosis. 189 15

A study of lymphocytic sub-populations of patients with rheumatoid arthritis, their families and partners, is presented. The determination was carried out by means of monoclonal antibodies, analysing: T cells sub-population (CD3, CD4, CD8 and quotient CD4/CD8); B cells sub-population (B1); activated cells (OK1a); monocytes and NK cells (OKM1 and BMA 070). The results showed an increase of CD3 sub-population (T total lymphocytes) in patients with RA and their families. The meaning of these results is difficult to evaluate as lymphocyte sub-population is affected by several variables. The lack of modification of suppressor population, CD4/CD8 quotient and IKM1 cells in RA patients is probably due to the moderate activity of the disease.
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PMID:[Lymphocyte subpopulations in rheumatoid arthritis patients, their relatives and spouses]. 191 68


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