Monoclonal antibody therapy in rheumatic disease.
In rheumatic disease, monoclonal antibodies have been used for the treatment of refractory rheumatoid arthritis, systemic lupus erythematosus, unresponsive vasculitis and relapsing polychondritis. Our greatest experience has however been with rheumatoid arthritis. After molecular engineering, hybrid monoclonal antibodies constructed from animal sources become largely human, and thus well tolerated, and highly specific. They can be focused selectively to particular targets, but the problem is to identify the causative antibody. In rheumatoid arthritis, we do know a great deal about the pathogenesis of the disease and rational 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. Despite 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 be a reasonable approach to monoclonal antibody therapy. Trials have been conducted using antibodies against the surface markers CD7, CD5, CDw52 and CD4. Further work has centered on differentiation antigens. Preliminary evidence suggests anti-interleukin-2-receptor monoclonal antibodies may be effective in rheumatoid arthritis. There have also been reports of attempts at anti-cytokine immunotherapy. Adhesion molecules would be another potential target. The ongoing trials have given us much insight into the pathogenesis of rheumatoid diseases and led us to the stage where we are now attempting to identify appropriate therapeutic regimes and combinations to maximise patient benefit. At present, we must continue our research for the causative antigen.
Pitzalis
C
C
Rheumatology Unit, Guy's Hospital, London, United Kingdom.
Choy
E
E
Kingsley
G
G
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D015703:Antigens, CD / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000276:immunology
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2