COMPLEMENT FIXATION IN DISEASED TISSUES I. FIXATION OF GUINEA PIG COMPLEMENT IN SECTIONS OF KIDNEY FRO~[ HUMANS WITH MEMBRANOUS GLOMERULONEPttRITIS AND RATS INJECTED WITH ANTI-RAT KIDNEY SERUM*~ BY

The means by which interaction of antigen and antibody may lead to disease is not well understood. Arthus (1) observed that repeated subcutaneous injections of horse serum in rabbits elicited progressively severe local inflammatory reaction. From clinical observations on serum disease in man yon Pirquet (2) suggested "that a disease might be due indirectly to an antibody" and he coined the term allergy to mean "a changed reactivity" that occurs as a result of the injection of foreign serum or exposure to other antigenic substances. Schick (3), impressed by the similarity of some of the manifestations of serum disease to the Nachkrankheiter~ of scarlet fever, suggested that the latter were allergic reactions. From experiments on local anaphylaxis, as seen in the Arthus phenomenon, Opie (4) concluded that the cutaneous inflammatory reaction is a result of antigen meeting with antibody in the tissues. For many years it has been suggested and recently emphasized that antibodies may arise to antigenic components of an individual's own tissues and produce cytotoxic effects (5, 6). To elucidate the role of antibodies and allergic reactions in disease it would seem important to identify antigen-antibody complexes in tissues. Globulin of anti-kidney serum has been demonstrated in glomeruli of animals injected with nephrotoxic antiserum (7, 8). Human globulin has been identified in renal glomeruli of patients with a variety of diseases affecting the kidneys (9-11). In these investigations the deposits of globulin, identified by means of the fluorescent antibody technique, have been interpreted as antibodies localized in glomerular capillary walls. However, it cannot be concluded from the immunohistologic investigations on human tissues that the deposits of globulin represent antibody in combination with antigen.