Idiotypic induction of autoimmunity: a new aspect of the idiotypic network

Three different experimental models of autoimmune diseases were induced in naive mice after idiotypic immunization. 1) systemic lupus erythematosus (SLE) after injection of anti-DNA antibodies carrying the pathogenic Id-16/6; 2) anti-phospholipid syndrome (APLS) after immunization with anti-cardiolipin antibodies (having the pathogenic H-3 and MIV-7 Ids); and 3) Wegener's granulomatosis (WG) induced with anti-neutrophile cytoplasmic antibodies (ANCA). In all three experiments the mice developed the respective anti-Id antibodies (Ab2), and, after a follow-up period of 4-8 months anti-anti-Id (Ab3) were generated by the immunized mice. The latter antibodies (Ab3) had the binding characteristics of the respective autoantibodies (Ab1) used in the first immunization. The appearance of auto-antibodies in the sera of the mice was associated with emergence of all the typical clinical and laboratory findings seen in patients with SLE, APLS, and WG, respectively. We suggest that in some autoimmune diseases, especially in those in which the presumed autoantigen is not immunogenic (e.g., DNA, cardiolipin), the disease may follow a common infection: The antibodies against the infecting agent may carry a pathogenic idiotype of a specific autoantibody. In a subject prone to autoimmunity (genetic, hormonal, immunologic factors), the pathogenic idiotype will progress in dysregulating the immune system to evolve into a clinical overt autoimmune disease.