Antibodies to Ribosomal P Proteins of Trypanosoma cruzi in Chagas Disease Possess Functional Autoreactivity with Heart Tissue and Differ from Anti-P Autoantibodies in Lupus

• Published in: Proceedings of the National Academy of Sciences - PNAS 1997-09, Vol.94 (19), p.10301-10306
• Main Authors: Kaplan, Dan, Ferrari, Ines, Bergami, Pablo Lopez, Mahler, Evelina, Levitus, Gabriela, Chiale, Pablo, Hoebeke, Johan, Marc H. V. Van Regenmortel, Levin, Mariano J.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Antibodies; Antibodies, Protozoan - immunology; Antibody Specificity; Autoantibodies; Autoantibodies - immunology; Biological Sciences; Cardiovascular disease; Cardiovascular diseases; Chagas Cardiomyopathy - immunology; Chagas disease; Epitopes; Humans; Immunity (Disease); Infections; Lupus Erythematosus, Systemic - immunology; Medical research; Molecular Sequence Data; Myocardium; Myocardium - immunology; Parasites; Peptides; Proteins; Protozoan Proteins; Reactivity; Receptors; Ribosomal Proteins - immunology; Trypanosoma cruzi; Trypanosoma cruzi - immunology; Vector-borne diseases
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.19.10301

Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) 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 (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the β1-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the β1adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-β1receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergicstimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.