The pathogenesis of autoimmune diseases

Autoimmunopathies are chronic inflammatory diseases which can be subdivided into several specificities on the ground of the clinical picture as well as serological findings and involvement of organ systems like the kidney, central nervous system or the hematopoietic system. The pathogenesis of these diseases is incompletely understood. With the exception of rare diseases in which the autoantigens are known, in the most frequent autoimmunopathies like rheumatoid arthritis or Systemic Lupus Erythematosus (SLE) only some partial aspects of the pathogenetic scenario are understood and rather well substantiated by experimental data. In RA, there are controversies concerning the central involvement of T-lymphocytes and/or synovial fibroblasts in the initiation of the diseases. It is meanwhile well known that TNF-alpha and possibly other related cytokines are involved at least in the perpetuation of the inflammatory cascades. Specific blockade of TNF-alpha leads to rapid improvement of RA disease activity and can prevent tissue destruction. An intriguing hypothesis postulates a central role for a dysregulated apoptosis in the development of SLE. In this review we will concentrate on pathogenetic concepts of autoimmune diseases as exemplified by RA and SLE.