Idiotypic induction of autoimmunity: do we need an autoantigen?

Autoimmune diseases may be classified into two groups: autoantibody-mediated and cellular-mediated. In many autoimmune conditions the autoantigen is well-defined, immunogenic and, upon immunization of the naive animal, will lead to the production of autoantibodies and, eventually, to the induction of the respective autoimmune disease. However, in certain autoimmune diseases the autoantigen is either ill-defined, or is not immunogenic, or is intracellular. In many of these situations it is difficult to explain the emerging clinical findings by the mere binding of the autoantibody to the autoantigen. We herewith propose an additional mechanism for autoimmune disease induction, employing active idiotypic immunization. The induction of the disease is exemplified by three clinical models-SLE, APS, and Wegener's granulomatosis. The implications for human disease are discussed.