REDUCTION OF SYNOVIAL INFLAMMATION AFTER ANTI-CD4 MONOCLONAL-ANTIBODYTREATMENT IN EARLY RHEUMATOID-ARTHRITIS

Objective. To study the effect of chimeric anti-CD4 monoclonal antibod y (MAb) therapy on synovial inflammation, in order to interpret the cl inical experience with anti-CD4 treatment, Methods. The immunohistolog ic features of synovial biopsy specimens before and 4 weeks after anti -CD4 MAb (cM-T412) therapy were studied in patients with rheumatoid ar thritis, 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 dail y for 5 consecutive days. Results. Although the patients did not exper ience clinical improvement, significant decreases in the number of cir culating CD4+ cells, the degree of synovial inflammatory infiltration, and the mean scores for expression of adhesion molecules were found i n the 7 patients 4 weeks after receiving cM-T412. The scores for infil tration with CD4+ and other inflammatory cells were particularly reduc ed following treatment with either 25 mg or 50 mg cM-T412, Cytokines, such as interleukin-1 beta and tumor necrosis factor alpha, could stil l 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 thatCD4T cells orchestrate local cellular infiltration. The lack of clinical effect of anti-CD4 therapy might be explained by an insufficient decre ase in the number of synovial CD4+ cells and by the persistence of cyt okines. Determination of whether more adequate dosing would lead to a clinical improvement must await further study.