Objective. To study the effect of chimeric anti-CD4 monoclonal antibody (MAb) therapy on synovial inflammation, in order to interpret the clinical experience with anti-CD4 treatment.Methods. The immunohistologic features of synovial biopsy specimens before and 4 weeks after anti-CD4 MAb (cM-T412) therapy were studied in patients with rheumatoid arthritis. The patients received intravenous doses of either placebo (n = 1) or 10 mg (n = 4), 25 mg (n = 2), or 50 mg (n = 1) of cM-T412 daily for 5 consecutive days.Results. Although the patients did not experience clinical improvement, significant decreases in the number of circulating CD4+ cells, the degree of synovial inflammatory infiltration, and the mean scores for expression of adhesion molecules were found in the 7 patients 4 weeks after receiving cM-T412. The scores for infiltration with CD4+ and other inflammatory cells were particularly reduced following treatment with either 25 mg or 50 mg cM-T412. Cytokines, such as interleukin-lp and tumor necrosis factor a, could still be detected in the synovial tissue after treatment.Conclusion. The decline in the numbers of inflammatory cells and adhesion molecules in synovial tissue after CD4+ cell depletion supports the view that

Objective. To assess the efficacy of the CD4 monoclonal antibody (MAb) cM-T412 in the treatment of early rheumatoid arthritis (RA).Methods. Sixty patients were enrolled in a 6-week randomized, double-blind, placebo-controlled study investigating multiple dose regimens of cM-T412. Thirty patients subsequently were enrolled in a 9-month randomized, double-blind, placebo-controlled study investigating monthly single-dose adminiitrations of cM-T412.Results. Analysis of clinical parameters revealed no changes in arthritis activity in the groups that received CD4 MAb or the placebo group, and no difference between the groups, in either in the first or the second part of the study. The number of circulating CD4+ cells decreased substantially in the patients treated with CD4 MAb. Conclusion. CD4 MAb treatment of patients with early RA induced no therapeutic effect.Present understanding of the pathogenesis of rheumatoid arthritis (RA) is incomplete. However, accumulating evidence has indicated that the T lymphocyte orchestrates an autoimmune process (I). Therefore, surface antigens of T cells were suggested as possible targets for a specific immunotherapy .Monoclonal antibodies (MAb) against the CD4 molecule were shown to modulate the function of CD4+ T cells (2). Following the successful use of CD4 MAb in

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The recognition that certain monoclonal antibodies have immunosuppressive properties led to the therapeutic application in autoimmune rheumatic diseases, rheumatoid arthritis in particular. The therapeutic potential of monoclonal antibodies directed against cell surface antigens mainly present on T-cells has been suggested by open trials in rheumatoid arthritis but the results of controlled studies are disappointing. Open intervention studies with monoclonal antibodies directed at other antigens relevant for the rheumatoid inflammation such as the intercellular adhesion molecule ICAM-1 or the cytokines IL-6 and TNF alpha provided encouraging clinical improvements. The impressive potential of anti-TNF alpha which was already illustrated by the immediate suppression of the acute phase response in open studies could be confirmed by a recently completed controlled trial. The present overview summarizes the available information on the results of these treatment modalities and discusses the possibilities of monoclonal antibodies as a long term treatment for rheumatic diseases.