CARDIAC ANTIGEN-SPECIFIC AUTOANTIBODY PRODUCTION IS ASSOCIATED WITH CARDIOMYOPATHY IN TRYPANOSOMA-CRUZI-INFECTED MICE

An inflammatory cardiomyopathy may develop in humans and experimental animals with chronic Trypanosoma cruzi infection (Chagas' disease). Am ong the possible mechanisms involved in the pathogenesis of Chagas' ca rdiomyopathy, induction of heart-specific autoimmune responses has rec ently received substantial experimental support. The goal of the curre nt study was to determine whether cardiac Ag-specific antibodies are p roduced in T. cruzi-infected mice with heart disease and, if so, to de termine their Ag specificities. Upon infection with the Brazil strain of T. cruzi, C57BL/6 mice develop a cardiomyopathy that is histologica lly similar to that observed in chronically infected humans. Antisera from these mice were found to react with three cardiac Ag, having rela tive molecular masses of 200, 150, and 53 kDa. p200 and p150 are speci fically found in heart muscle, although p53 is found in skeletal muscl e as well. C57BL/6 mice infected with the Guayas strain of T. cruzi, w hich do not develop cardiomyopathy, did not produce antibodies to p200 , p150, or p53, indicating that these antibodies may be specific marke rs of cardiomyopathy. Finally, p200 and p53 were identified as the con tractile protein myosin and the intermediate filament protein desmin, respectively. This last finding is of special interest, because antibo dies specific for myosin or desmin have been detected in humans and ex perimental animals with other natural and experimental cardiomyopathie s. This suggests that infection with particular strains of T. cruzi ma y lead to the development of a cardiac Ag-specific autoimmune disease, possibly involving one or more of the Ag identified in this study.