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 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 β1 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-β1 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.
Registro:
Documento: |
Artículo
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Título: | 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 |
Autor: | Kaplan, D.; Ferrari, I.; Bergami, P.L.; Mahler, E.; Levitus, G.; Chiale, P.; Hoebeke, J.; Van Regenmortel, M.H.V.; Levin, M.J. |
Filiación: | Lab. Biol. Molec. Enfermedad Chagas, Inst. Invest. Ing. Genetica B., University of Buenos Aires, 1428 Buenos Aires, Argentina Cardiovascular Division, Ramos Mejía Hospital, 1221 Buenos Aires, Argentina Equipe d'Immunologie des Recepteurs, C-JF93-09 l'Inst. Natl. S. Rech. M., F-37032 Tours, France Inst. de Biol. Molec. et Cellulaire, Ctr. Natl. de la Rech. Scientifique, 67084 Strasbourg, France Inst. Invest. Ing. Genetica y B., Vta Obligado 2490, 1428 Buenos Aires, Argentina
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Palabras clave: | antibody response; antigen recognition; article; autoimmunity; carboxy terminal sequence; cell infiltration; chagas disease; heart muscle cell; host parasite interaction; human; human cell; immune response; lupus erythematosus; mononuclear cell; priority journal; trypanosoma cruzi; Amino Acid Sequence; Animals; Antibodies, Protozoan; Antibody Specificity; Autoantibodies; Chagas Cardiomyopathy; Humans; Lupus Erythematosus, Systemic; Molecular Sequence Data; Myocardium; Protozoan Proteins; Ribosomal Proteins; Trypanosoma cruzi; Trypanosoma; Trypanosoma cruzi |
Año: | 1997
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Volumen: | 94
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Número: | 19
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Página de inicio: | 10301
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Página de fin: | 10306
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DOI: |
http://dx.doi.org/10.1073/pnas.94.19.10301 |
Título revista: | Proceedings of the National Academy of Sciences of the United States of America
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Título revista abreviado: | PROC. NATL. ACAD. SCI. U. S. A.
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ISSN: | 00278424
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CODEN: | PNASA
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CAS: | Antibodies, Protozoan; Autoantibodies; L12E protein, Trypanosoma cruzi; Protozoan Proteins; Ribosomal Proteins
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v94_n19_p10301_Kaplan |
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Citas:
---------- APA ----------
Kaplan, D., Ferrari, I., Bergami, P.L., Mahler, E., Levitus, G., Chiale, P., Hoebeke, J.,..., Levin, M.J.
(1997)
. 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. Proceedings of the National Academy of Sciences of the United States of America, 94(19), 10301-10306.
http://dx.doi.org/10.1073/pnas.94.19.10301---------- CHICAGO ----------
Kaplan, D., Ferrari, I., Bergami, P.L., Mahler, E., Levitus, G., Chiale, P., et al.
"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"
. Proceedings of the National Academy of Sciences of the United States of America 94, no. 19
(1997) : 10301-10306.
http://dx.doi.org/10.1073/pnas.94.19.10301---------- MLA ----------
Kaplan, D., Ferrari, I., Bergami, P.L., Mahler, E., Levitus, G., Chiale, P., et al.
"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"
. Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 19, 1997, pp. 10301-10306.
http://dx.doi.org/10.1073/pnas.94.19.10301---------- VANCOUVER ----------
Kaplan, D., Ferrari, I., Bergami, P.L., Mahler, E., Levitus, G., Chiale, P., et al. 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. PROC. NATL. ACAD. SCI. U. S. A. 1997;94(19):10301-10306.
http://dx.doi.org/10.1073/pnas.94.19.10301