A Theory concerning the Mechanism of Allergic Diseases.

The causes of human glomerular nephritis and nephrosis usually have been considered to involve an allergic mechanism. Both diseases occur more commonly in those who have other manifestations of allergy, often members of families with an allergic diathesis. Acute nephritis usually follows infection with certain strains of hemolytic streptococcus, ' with a latent period like that which would be necessary for antibody formation. During the nephrotic stage of glomerular nephritis the serum complement level falls precipitously, then rises as the nephrotic activity subsides.2 Some have attributed nephritis to the immunologic effects of a hypothetical autogenous antibody to kidney tissue,3 but the demonstration of autoantibodies to kidney tissue has been elusive.4 There has always been a stumbling block in this explanation: Why should an autogenous tissue ever become antigenic? The association of streptococcal infection with nephritis has been invoked to overcome this stumbling block, and the antigenicity of autogenous kidney protein has been attributed to some interaction with streptococcal protein.2' 5 Experiments to find out whether such an interaction can create autogenous or even homologous antigenicity have led to doubtful or negative conclusions.5 6 Two types of experimental immunologic procedure will produce nephritis in animals. In one type, usually called "Masugi-type nephritis" (although the work of Masugi7 was antedated by that of Lindemann8 as well as by that of Wilson and Oliver,9), antikidney antibodies are formed in a heterologous species and then administered to produce nephritis in experimental animals. Obviously, this mechanism cannot be the natural one involved in the production of human nephritis. The second type of experimental nephritis is produced by administration of various foreign proteins, not themselves antibodies or extracted from kidney tissues.°0' 11, 12 Hawn and Janeway speculated provocatively concerning the reason why such foreign proteins, not themselves directly related to or derived from the kidney, should have the capacity to induce nephritis. 10 In 1940 Kay observed that experimental nephritis in the rabbit followed a latent period after the administration of duck anti-rabbit-kidney serum and that the development of nephritis came simultaneously with appearance in the rabbit serum of antibodies to duck serum.'3 Indeed, he suggested that the duck anti-rabbitkidney antibody combines with rabbit kidney tissue to produce a harmless combination (DAK-RK) which is fixed in the kidney tissue and that the rabbit antiduck-serum antibodies, when formed, then combine with the harmless DAK-RK combination to produce a harmful antigen-antibody complex, which causes nephritis. Both types of experimental nephritis may be inhibited or enhanced by general factors affecting the response to any antigen-antibody reaction (state of adrenal function, 14 complement availability,'5 etc.). Kay's experiment may be considered as a special case of the second type of experimental nephritis, since the specific antikidney antibody produced no immediate effect, possibly as the result of a low antibody titer, and the subsequent nephritis seemed to result from the foreign character of duck serum protein.