[New treatments of rheumatoid arthritis for future use]

Rheumatoid arthritis is a common autoimmune disorder for which current treatments are unsatisfactory since they usually fail to control joint destruction. Pathophysiological mechanisms are incompletely understood but T-lymphocytes and antigen-presenting cells play a key role. Novel therapeutic approaches are directed to these cell types via the trimolecular T-cell receptor-major histocompatibility complex molecules-peptide (TCR-MHC-peptide) complex and other molecules involved in lymphocyte activation. The goal is to restore tolerance through highly selective immunosuppression to minimize adverse effects. Monoclonal antibodies (Ab) directed against a number of targets are potent tools. Antibodies to CD5, CD7, CD54 and CDw52 act on the overall T-cell population. Antibodies against CD4, CD25 or HLA-DR produce more limited immunomodulatory effects. Most human studies to date are encouraging but not controlled study has yet been published. The most satisfactory therapeutic approach involves restoration of tolerance through inhibition of auto-immune T-cell clones. The existence of these clones has been demonstrated in animal models of autoimmune diseases. Successfully developed, highly specific immunological tools include anti-clonotypic monoclonal antibodies, peptide analogs, and anti-T-cell vaccines. The extrapolation to human disease of insights acquired in animal models and the feasibility of these novel therapeutic approaches in rheumatoid arthritis patients are discussed.