Involvement of CD40-CD154 interaction in immunopathogenesis of collagen diseases and its application to a novel therapeutic strategy

Abstract

CD40 and CD154 belong to the tumor necrosis factor (TNF) receptor superfamily and the TNF superfamily, respectively. Evidence is accumulating that indicates the importance of this receptor-ligand pair in the immunopathogenesis of autoimmune diseases. The CD40-CD154 interaction influences antigen presentation, tolerance, autoantibody production and tissue damage, all of which are relevant to the development and perpetuation of autoimmune diseases. Among the collagen diseases, the CD40-CD154 interaction has been intensively investigated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). In this article, both basic and clinical research suggesting the involvement of the CD40-CD154 interaction in SLE, RA, inflammatory myopathies, systemic sclerosis and antiphospholipid syndrome are reviewed. The results of clinical trials from CD40-CD154 blockade are also analyzed. CD40-CD154 blockade in animal models of autoimmune diseases has been reported to be a promising novel therapeutic approach and, thus, has attracted great attention from pharmaceutical companies. However, the development of CD40-CD154 blockers with both significant clinical efficacy and safety has not been successful and research advances in this field are eagerly awaited. © 2004, The Japan Society for Clinical Immunology. All rights reserved.