Autoantibodies--antigen driven or idiotypically induced.

The current acceptable notion regarding autoimmune diseases is that autoimmunity and autoimmune diseases are autoantigen driven. This pathogenetic mechanism is very much conceivable according to theories in classical immunology, namely, if there is a ”reactive” antibody, it must have been generated upon immunization with an antigen. Definitely, a support to this notion is gained from the fact some of the autoantibodies do bind specifically to autoantigens (one can refer to them as target — thus assuming that the binding ligands are also the driving autoantigens). In some of the cases (e.g. acetylcholine receptor in MG or gpIIb in ITP) there is a rational pathogenetic mechanism to explain the autoimmune attack in the specific autoimmune disease. Further support to the (auto)antigen driven theory comes from sequence analyses of nucleotides of autoantidoby Igs structure (especially in the CDR3) demonstrating somatic mutation, thus pointing to an antigen driven mechanism. To explain the sudden loss of tolerance to self antigens a linear or conformational changes in the autoantigens were proposed. More complex explanations were given to presumed intracellular and intranuclear autoantigens (e.g. DNA, nucleosoures, PDH etc.). In those cases there was a prerequisite necessity to explain their exposure to the immune system. In each one of these intracellular autoantigens it has been proposed that they are exposed to the immune cells on the surface of the respective cells, thus being able to stimulate the immunoreactive cells on the one hand, and being targets to the immune effector cells and antibodies on the other hand. In the current article I would like to propose that in some autoimmune diseases and especially in the multisystem non-organ specific ones, in which characteristic and specific autoantibodies to ubiquitous autoantigen were found (DNA/SLE, RNP/MCTD, PDH/ PBC etc.), there is no driven autoantigen. Furthermore, binding of these existing serum autoantibodies to a presumed ubiquitous autoantigen, not necessarily means that the specific, multiorgan