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
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 EESDDDMG...
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todo:paper_00278424_v94_n19_p10301_Kaplan2023-10-03T14:38:20Z 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 Kaplan, D. Ferrari, I. Bergami, P.L. Mahler, E. Levitus, G. Chiale, P. Hoebeke, J. Van Regenmortel, M.H.V. Levin, M.J. 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 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00278424_v94_n19_p10301_Kaplan |
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Universidad de Buenos Aires |
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I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Kaplan, D. Ferrari, I. Bergami, P.L. Mahler, E. Levitus, G. Chiale, P. Hoebeke, J. Van Regenmortel, M.H.V. Levin, M.J. 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Kaplan, D. Ferrari, I. Bergami, P.L. Mahler, E. Levitus, G. Chiale, P. Hoebeke, J. Van Regenmortel, M.H.V. Levin, M.J. |
| author_facet |
Kaplan, D. Ferrari, I. Bergami, P.L. Mahler, E. Levitus, G. Chiale, P. Hoebeke, J. Van Regenmortel, M.H.V. Levin, M.J. |
| author_sort |
Kaplan, D. |
| 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 |
| title_short |
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 |
| title_full |
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 |
| title_fullStr |
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 |
| title_full_unstemmed |
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 |
| title_sort |
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 |
| url |
http://hdl.handle.net/20.500.12110/paper_00278424_v94_n19_p10301_Kaplan |
| work_keys_str_mv |
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