A study of the pathogenesis of rheumatic fever, glomerulonephritis and other autoimmune diseases triggered by infection.

Inherited autoimmune disease appears to be due to a genetic defect which permits the formation of forbidden clones of antibody-forming cells. There is evidence that separate pathogenic and non-pathogenic autoantibodies occur, and that the former are directly responsible for the lesions of autoimmune disease. The observed initiation and aggravation of autoimmunity by tissue damage, including that inflicted by microbial infection, indicates that autoantigens in undamaged tissues are partially or completely inactive, as regards ability to stimulate autoantibody formation, even in people possessing the appropriate forbidden clones. Heterophile phenomena indicate that invading micro-organisms will sometimes carry antigens which are present in the host. If the appropriate forbidden clone is present, autoantibody formation will be stimulated. This mechanism appears to be particularly probable in rheumatic fever and glomerulonephritis. To avoid the inadvertent triggering of autoimmune disease in susceptible subjects, vaccines should be free of human antigens.