Preliminary evidence for idiotype-antiidiotype immune complexes cross-reactive with lymphocyte antigens in AIDS and...

Several investigators have proposed that autoimmunity may be induced by idiotype-antiidiotype antibody networks. It is generally assumed that the antiidiotype is produced in response to the idiotype, and therefore that autoimmune diseases have single antigenic initiators. The theory of multiple-antigen-mediated autoimmunity (MAMA) proposes, on the other hand, that idiotype and antiidiotype result from two primary immune responses to two chemically complementary antigens. Because of the complementarity of the antigens, and the complementarity of the antibodies for the antigens, the antibodies will themselves be complementary. They will thus form circulating immune complexes, the self-nonself distinction diffusion (DAD) experiments (a modification of Ouchterlony immunodiffusion), in which 1800 pairs of antibodies were screened for their ability to form precipitating complexes. Four sets of antibodies associated with AIDS (HIV + Staphylococcus; HIV + Mycoplasma; CMV + Mycoplasma; and HBV + Mycoplasma) specifically precipitated each other, and one of the antibodies in each set also precipitated monoclonal antibodies against one or more lymphocyte protein markers. These results therefore demonstrate that idiotype-antiidiotype antibodies can be elicited by independent antigens and may induce AIDS-related forms of autoimmunity directed at lymphocytes.