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-1 beta and tumor necrosis factor alpha, 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 CD4+ T cells orchestrate local cellular infiltration. The lack of clinical effect of anti-CD4 therapy might be explained by an insufficient decrease in the number of synovial CD4+ cells and by the persistence of cytokines. Determination of whether more adequate dosing would lead to a clinical improvement must await further study.
RCT Entities:
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-1 beta and tumor necrosis factor alpha, 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 CD4+ T cells orchestrate local cellular infiltration. The lack of clinical effect of anti-CD4 therapy might be explained by an insufficient decrease in the number of synovial CD4+ cells and by the persistence of cytokines. Determination of whether more adequate dosing would lead to a clinical improvement must await further study.
Authors: Z N Jahangier; J W G Jacobs; M C Kraan; M J G Wenting; T J Smeets; J W J Bijlsma; F P J G Lafeber; P P Tak Journal: Ann Rheum Dis Date: 2006-04-20 Impact factor: 19.103
Authors: J J Haringman; D M Gerlag; A H Zwinderman; T J M Smeets; M C Kraan; D Baeten; I B McInnes; B Bresnihan; P P Tak Journal: Ann Rheum Dis Date: 2004-12-02 Impact factor: 19.103
Authors: M D Smith; D Baeten; A-K Ulfgren; I B McInnes; O Fitzgerald; B Bresnihan; P P Tak; D Veale Journal: Ann Rheum Dis Date: 2005-06-23 Impact factor: 19.103