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). Among the possible mechanisms involved in the pathogenesis of Chagas' cardiomyopathy, induction of heart-specific autoimmune responses has recently received substantial experimental support. The goal of the current study was to determine whether cardiac Ag-specific antibodies are produced in T. cruzi-infected mice with heart disease and, if so, to determine their Ag specificities. Upon infection with the Brazil strain of T. cruzi, C57BL/6 mice develop a cardiomyopathy that is histologically similar to that observed in chronically infected humans. Antisera from these mice were found to react with three cardiac Ag, having relative molecular masses of 200, 150, and 53 kDa. p200 and p150 are specifically found in heart muscle, although p53 is found in skeletal muscle as well. C57BL/6 mice infected with the Guayas strain of T. cruzi, which do not develop cardiomyopathy, did not produce antibodies to p200, p150, or p53, indicating that these antibodies may be specific markers of cardiomyopathy. Finally, p200 and p53 were identified as the contractile protein myosin and the intermediate filament protein desmin, respectively. This last finding is of special interest, because antibodies specific for myosin or desmin have been detected in humans and experimental animals with other natural and experimental cardiomyopathies. This suggests that infection with particular strains of T. cruzi may lead to the development of a cardiac Ag-specific autoimmune disease, possibly involving one or more of the Ag identified in this study.
Tibbetts
R S
RS
Department of Pathology, Northwestern University, Chicago, IL 60611.
McCormick
T S
TS
Rowland
E C
EC
Miller
S D
SD
Engman
D M
DM
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D009202:Cardiomyopathies / Q000276:immunology* / Q000473:pathology; D002598:Chagas Cardiomyopathy / Q000276:immunology* / Q000473:pathology; D003893:Desmin / Q000276:immunology; D005260:Female; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009132:Muscles / Q000276:immunology; D009206:Myocardium / Q000276:immunology* / Q000473:pathology; D009218:Myosins / Q000276:immunology; D014349:Trypanosoma cruzi
D001323:Autoantibodies; D001324:Autoantigens; D003893:Desmin; D009218:Myosins