Antibodies to Ribosomal P Protein of Trypanosoma Cruzi in Chagas' Disease Possess Functional Autorreactivity with Heart Tissue and Differ from Anti P Autoantibodies in Lupus

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Abstract

Anti-Pantibodies present in sera from patients withchronic Chagas heart disease recognize peptide R13,EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13, EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus and with the acidicepitope, AESDE, of the second extracelular loop of the (31-adrenergic receptor. Anti P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomalP proteins and peptides, and parasite ribosomal P proteins and peptides to the same extend. A semiquantitative estimation of the binding of chronic Chagas heart disease anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5times higher for R13 than forH13. Competitive enzyme immunoassays demonstrated that chronic Chagas heart disease anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracelular loop of the (31 adrenoreceptor. Anti-P antibodies isolated from chronic Chagas heart disease patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-(31receptor antibodies isolated from the same patient.In contrast, systemic lupus erythematosus anti P autoantibodies have no functional effect. Our results suggest that the adrenergic stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in chronic Chagas heart disease.