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Sera from patients with chronic Chagas heart disease recognize the carboxyl-terminal regions of the Trypanosoma cruzi ribosomal P proteins defined by B cell epitopes P013 (EDDDDDFGMGALF) and R13 (EEEDDDMGFGLFD) corresponding to the T. cruzi ribosomal P0 (TcP0) and P2β (TcP2β) proteins, respectively. It has been hypothesized that both epitopes may induce antibodies that cross-react and stimulate the β1-adrenoreceptor. However, no proof as to their pathogenicity has been obtained. We investigated the consequences of immunizing mice with either TcP0 or TcP2β proteins. Of 24 immunized animals, 16 generated antibodies against the carboxyl-terminal end of the corresponding protein, 13 of which showed an altered ECG (P<0.001, 81%). Immunization with TcP0 induced anti-P013 antibodies that bind to and stimulate cardiac G-protein-coupled receptors and are linked to the induction of supraventricular arrhythmia, repolarization, and conduction abnormalities as monitored by serial electrocardiographic analysis. In contrast, immunization with TcP2β generated anti-R13 antibodies with an exclusive β1-adrenergic-stimulating activity whose appearance strictly correlated with the recording of supraventricular tachycardia and death. These findings demonstrate that anti-P antibodies are arrhythmogenic in the setting of a normal heart, since no inflammatory lesions or fibrosis were evident to light microscopic examination.


Documento: Artículo
Título:Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic
Autor:Lopez Bergami, P.; Scaglione, J.; Levin, M.J.
Filiación:Lab. Biol. Molec. Enferm. de Chagas, INGEBI, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina
Palabras clave:β1-adrenoreceptor; Arrhythmia; Chagas disease; G-protein-coupled receptors; Supraventricular tachycardia; beta 1 adrenergic receptor; cross reacting antibody; G protein coupled receptor; glycine cleavage system; immunoglobulin G; protozoon antibody; ribosome protein; synthetic peptide; adolescent; animal cell; animal model; antigenicity; arrhythmogenesis; article; carboxy terminal sequence; Chagas disease; controlled study; electrocardiography; epitope mapping; heart arrhythmia; human; humoral immunity; immunization; mouse; nonhuman; pathogenicity; priority journal; supraventricular tachycardia; Trypanosoma cruzi; Alanine; Amino Acid Sequence; Animals; Antibodies, Protozoan; Antibody Formation; Carrier Proteins; Chagas Cardiomyopathy; Cloning, Molecular; COS Cells; Electrocardiography; Epitope Mapping; Glutathione Transferase; Heart Rate; Humans; Immunization; Immunoglobulin G; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Mutagenesis; Myocardium; Protozoan Proteins; Rats; Recombinant Fusion Proteins; Ribosomal Proteins; Trypanosoma cruzi; Animalia; Protozoa; Trypanosoma; Trypanosoma cruzi
Página de inicio:2602
Página de fin:2612
Título revista:FASEB Journal
Título revista abreviado:FASEB J.
CAS:Alanine, 56-41-7; Antibodies, Protozoan; Carrier Proteins; Glutathione Transferase, EC; Immunoglobulin G; L12E protein, Trypanosoma cruzi; maltose-binding protein; Protozoan Proteins; Recombinant Fusion Proteins; Ribosomal Proteins


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---------- APA ----------
Lopez Bergami, P., Scaglione, J. & Levin, M.J. (2001) . Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic. FASEB Journal, 15(14), 2602-2612.
---------- CHICAGO ----------
Lopez Bergami, P., Scaglione, J., Levin, M.J. "Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic" . FASEB Journal 15, no. 14 (2001) : 2602-2612.
---------- MLA ----------
Lopez Bergami, P., Scaglione, J., Levin, M.J. "Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic" . FASEB Journal, vol. 15, no. 14, 2001, pp. 2602-2612.
---------- VANCOUVER ----------
Lopez Bergami, P., Scaglione, J., Levin, M.J. Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic. FASEB J. 2001;15(14):2602-2612.