Common infections, idiotypic dysregulation, autoantibody spread and induction of autoimmune diseases

A new theory to explain the pathogenesis of autoimmune diseases is proposed. It is based on the idiotypic network and does not replace other existing theories of autoimmunity. It sets out to explain the emergence of some autoimmune conditions in which the proposed autoantigen is nonimmunogenic or is not identified at all. The theory is based on a series of experiments in which several experimental autoimmune diseases were induced in naive mice following active immunization with pathogenic idiotypes of autoantibodies. Following immunization with Ab(1) (Id) and production of Ab(2) (anti-Id), the mice developed Ab(3) (anti-anti-Id) having the original autoantibody characteristics and were associated with the respective serological and clinical manifestations of the disease. The human counterpart entails infection with common pathogen. Among the anti-pathogen antibodies generated, some carry idiotypes of autoantibodies. In healthy subjects with no risk factors for autoimmunity (e.g. complement or IgA def, males, normal Ts) the idiotypic cascade ends with Ab(2) (anti-Id). In subjects prone to autoimmune, Ab(3) (e.g. autoantibodies) develop and may be associated with respective clinical manifestations. (C) 1996 Academic Press Limited