title: 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.
abstract: 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 beta1-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 beta1 adrenoreceptor. 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-beta1 receptor antibodies isolated from the same patient. In contrast, SLE 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 cChHD.
authors.affiliation: Instituto de Investigaciones en Ingenieria Genetica y Biologia Molecular-Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Facultad de Ciencias Exactas y Naturales-University of Buenos Aires, Argentina.
authors.forename: D
authors.initials: D
authors.lastname: Kaplan
authors.forename: I
authors.initials: I
authors.lastname: Ferrari
authors.forename: P L
authors.initials: PL
authors.lastname: Bergami
authors.forename: E
authors.initials: E
authors.lastname: Mahler
authors.forename: G
authors.initials: G
authors.lastname: Levitus
authors.forename: P
authors.initials: P
authors.lastname: Chiale
authors.forename: J
authors.initials: J
authors.lastname: Hoebeke
authors.forename: M H
authors.initials: MH
authors.lastname: Van Regenmortel
authors.forename: M J
authors.initials: MJ
authors.lastname: Levin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology*; D002598:Chagas Cardiomyopathy / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008969:Molecular Sequence Data; D009206:Myocardium / Q000276:immunology*; D015800:Protozoan Proteins; D012269:Ribosomal Proteins / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D001323:Autoantibodies; C064601:L12E protein, Trypanosoma cruzi; D015800:Protozoan Proteins; D012269:Ribosomal Proteins