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Antibodies against the carboxyl‐terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic
Author(s) -
Bergami Pablo López,
Scaglione Jorge,
Levin Mariano Jorge
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0132com
Subject(s) - epitope , trypanosoma cruzi , antibody , chagas disease , autoantibody , immunization , biology , immunology , ribosomal protein , microbiology and biotechnology , virology , medicine , rna , biochemistry , ribosome , parasite hosting , world wide web , computer science , gene
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 (EFGMGALF) and R13 (EEEDDDMGFGLFD) corresponding to the T. cruzi ribosomal P0 (TcP0) and P2ß (TcP2ß) proteins, respectively. It has been hypothesized that both epitopes may induce antibodies that cross‐react and stimulate the ß 1‐adrenoreceptor. However, no proof as to their pathogenicity has been obtained. We investigated the consequences of immunizing mice with either TcP0 or TcP2ß 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, repolar‐ization, and conduction abnormalities as monitored by serial electrocardiographic analysis. In contrast, immunization with TcP2ß generated anti‐R13 antibodies with an exclusive ß1‐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.—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. 15, 2602–2612 (2001)