MONOCLONAL-ANTIBODY THERAPY IN RHEUMATIC DISEASE

In rheumatic disease, monoclonal antibodies have been used for the tre atment of refractory rheumatoid arthritis, systemic lupus erythematosu s, unresponsive vasculitis and relapsing polychondritis. Our greatest experience has however been with rheumatoid arthritis. After molecular engineering, hybrid monoclonal antibodies constructed from animal sou rces become largely human, and thus well tolerated. and highly specifi c. They can be focused selectively to particular targets, but the prob lem is to identify the causative antibody. In rheumatoid arthritis, we do know a great deal about the pathogenesis of the disease and ration al targets can be selected. The major histocompatibility complex class II molecules would theoretically be the most effective target, but no specific antigen has been identified. Total blockade of all class II molecules would probably result in unacceptable immunosuppression. Des pite this handicap, anti-HLA-DR4 monoclonal antibodies have been used in humans in an attempt to generate an anti-idiotypic response against DR4. T lymphocytes are known to play a major role in the pathogenesis of rheumatoid arthritis, thus targeting their surface markers would b e a reasonable approach to monoclonal antibody therapy. Trials have be en conducted using antibodies against the surface markers CD7, CD5, CD w52 and CD4. Further work has centered on differentiation antigens. Pr eliminary evidence suggests anti-interleukin-2-receptor monoclonal ant ibodies may be effective in rheumatoid arthritis. There have also been reports of attempts at anti-cytokine immunotherapy. Adhesion molecule s would be another potential target. The ongoing trials have given us much insight into the pathogenesis os rheumatoid diseases and led us t o the stage where we are now attempting to identify appropriate therap eutic regimes and combinations to maximise patient benefit. At present , we must continue our research for the causative antigen.