Monoclonal antibody therapy of rheumatoid arthritis

Abstract

Objectives. To (a) determine the immunological effects of a PRIMATIZED® anti-CD4 antibody alone or in combination with methotrexate in RA patients, (b) determine the immunological effects of a chimeric anti-CD25 antibody in RA patients who are partially refractive to methotrexate and (c) compare interleukin-15 levels in the serum of RA patients and healthy controls and determine if there is a correlation between this cytokine and serum TNF-α, CD 122 expression, and disease activity. Patients and methods. (a) Eight RA patients were selected, four received anti-CD4+ placebo and the other four received anti-CD4+ methotrexate for 4 weeks. The immunological effects were assessed on peripheral blood by flow cytometry and thymidine incorporation assays. (b) Six RA patients were given anti-CD25 antibody (0.02-60mg) along with methotrexate for 26 days. The immunological effects were assessed on peripheral blood by flow cytometry, thymidine assays, and ELISA. (c) Blood and disease activity from twenty-one RA patients were obtained and serum IL-15 and TNF-α levels were measured by ELISA. IL-15R β chain (CD 122) expression was measured by flow cytometry. Results. (a) The anti-CD4 antibody caused a selective and significant decrease in the number of CD4+ T cells. No inhibition of PHA or mitogenic antibody stimulated proliferation was observed. (b) The anti-CD25 antibody caused a significant decrease in the percent CD25+ cells. The antibody bound CD25 and prevented interaction of IL-2 and IL-2R. Anti-CD25 antibody caused a significant decrease in PHA or mitogenic antibody stimulated proliferation. Clinically, the anti-CD25 antibody caused a significant decrease in the number of tender and swollen joints. (c) Elevated serum IL-15 was measured in 10 out of 21 RA patients but not in controls. No correlation was observed between IL-15 and TNF-α, CD122 expression or disease activity. Conclusions. (a) Methotrexate did not alter the effects of the PRIMATIZED® anti-CD4 antibody. Changes in antibody development processes have yielded two antibodies with different functions. (b) Anti-CD25 induced decrease in CD25+ T cells was associated with clinical benefit. The exact mechanisms of action are not clear. (c) Serum IL-15 levels in RA may be a more sensitive indicator of inflammation than TNF-α and may be a valuable tool in diagnosis.