Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic
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....
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todo:paper_08926638_v15_n14_p2602_LopezBergami2023-10-03T15:41:34Z Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic Lopez Bergami, P. Scaglione, J. Levin, M.J. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_08926638_v15_n14_p2602_LopezBergami |
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Universidad de Buenos Aires |
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I-28 |
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R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Lopez Bergami, P. Scaglione, J. Levin, M.J. Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Lopez Bergami, P. Scaglione, J. Levin, M.J. |
| author_facet |
Lopez Bergami, P. Scaglione, J. Levin, M.J. |
| author_sort |
Lopez Bergami, P. |
| title |
Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic |
| title_short |
Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic |
| title_full |
Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic |
| title_fullStr |
Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic |
| title_full_unstemmed |
Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic |
| title_sort |
antibodies against the carboxyl-terminal end of the trypanosoma cruzi ribosomal p proteins are pathogenic |
| url |
http://hdl.handle.net/20.500.12110/paper_08926638_v15_n14_p2602_LopezBergami |
| work_keys_str_mv |
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| _version_ |
1807320135244972032 |