Immunological follow-up of 17 patients with rheumatoid arthritis treated in vivo with an anti-T CD4+ monoclonal antibody (B-F5)
Seventeen patients with steroid-refractory rheumatoid arthritis were treated with a monoclonal antibody: anti-T CD4/B-F5 (IgG1) for 10 days. The daily dose was 20 mg. No severe side effects were observed and clinical improvement was seen in 15 patients, accompanied by a steep decline in C reactive protein levels. This improvement persisted as long as 12 months in 3 patients. A decline in lymphocyte counts was observed 2 hours after infusion. CD3+, CD4+, CD8+ and B cells were affected. Monocyte levels also decreased, whereas NK cell levels remained unchanged. After 24 hours a subsequent recovery of lymphocyte cell numbers made it possible to return to pre-treatment levels. Residual CD4+ cells coated with CD4 antibody were sporadically found even if residual antibody could be detected in the serum. These results indicate insufficient mAb concentrations. No patients developed detectable anti-mouse Ig antibodies during the treatment period, but 5 patients developed antibodies 15 to 30 days after the end of the treatment. Proliferative responses (mainly the response to ConA) were reduced at the end of the treatment. One month later the proliferative response returned to pre-treatment levels. mAb treatment did not induce long lasting cell activation, as indicated by the low levels of CD25+ or DR+ cells. Soluble IL2 receptor levels were significantly higher before treatment, but did not change after treatment. Soluble CD8 and soluble CD4 molecules were also more numerous before treatment and this increase was correlated with clinical parameters. Of interest was the correlation between the variations in soluble CD8 and the Ritchie index during treatment. The increased levels of serum TNF alpha and IL6 were not modified by treatment. A randomized study now appears necessary to prove the efficacy of the treatment. Such a study would also provide biological data and thus help to define factors predictive of a response in this heterogeneous disease.
Centre Régional de Transfusion Sanguine, Besancon, France.
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E
Racadot
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J
Wijdenes
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D
Wendling
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D002097:C-Reactive Protein / Q000032:analysis; D015704:CD4 Antigens / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D016827:CD8 Antigens / Q000097:blood; D005500:Follow-Up Studies; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D010865:Pilot Projects; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000648:ultrastructure; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D015850:Interleukin-6; D015375:Receptors, Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein