Reduction of Th1 cell activity in the peripheral circulation of patients with rheumatoid arthritis after treatment with a non-depleting humanized monoclonal antibody to CD4.
OBJECTIVE: To test the hypothesis that administration of a non-depleting monoclonal antibody (Mab) to CD4 may alter T cell function in patients with rheumatoid arthritis (RA), possibly associated with clinical benefit. METHODS: The patients with RA treated were a subset from a multicenter, placebo-controlled, randomized, double-blind trial and were randomized into one of 2 treatment groups receiving placebo or +/-450 mg of a humanized anti-CD4 Mab (ORTHOCLONE OKTcdr4a) per week for 2 treatment cycles. For the third cycle, patients who had received Mab during the first 2 courses were given placebo, whereas the patients who were originally given placebo received anti-CD4 Mab. To evaluate the impact of anti-CD4 Mab treatment on T cell functions, cytokine production by mitogen-stimulated peripheral blood T cells was monitored, cytokine mRNA levels were assessed in stimulated peripheral blood mononuclear cells (PBMC) by semiquantitative polymerase chain reaction, and clinical activity was also measured during the study. RESULTS: Administration of the anti-CD4 Mab, but not placebo, was followed by an immediate transient clinical benefit accompanied by a significant decrease in C-reactive protein levels. There was no significant change in the number of circulating CD4+ T cells. However, 7 weeks after the second Mab treatment, interleukin 2 (IL-2) and IFN-gamma mRNA levels were significantly reduced in all anti-CD4 Mab treated patients, but neither was reduced in placebo-treated patients. CONCLUSION: Clinical improvement in patients with RA treated with a non-depleting Mab to CD4 may be related to a decrease in the function of IL-2 and IFN-gamma producing Th1 cells.[1]References
- Reduction of Th1 cell activity in the peripheral circulation of patients with rheumatoid arthritis after treatment with a non-depleting humanized monoclonal antibody to CD4. Schulze-Koops, H., Davis, L.S., Haverty, T.P., Wacholtz, M.C., Lipsky, P.E. J. Rheumatol. (1998) [Pubmed]
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