Presence of antibodies to cardiac neuroreceptors in patients with Chagas disease
Keywords:
Chagas disease, Trypanosoma cruzi, receptors, muscarinic, pacemaker, artificial, antibodies, heart
Abstract
Introduction. The presence of antibodies against cardiac neuroreceptors has been established in several kinds of heart diseases as well as in Chagas disease. The antibody type most frequently identified is that which recognizes the muscarinic acetyl choline receptor type II (anti-m2MAChR).Objective. The frequency of the anti-m2MAChR was determined in a group of Colombian patients with permanent pacemaker implantation and Chagas disease.
Materials and methods. Fifty-two patients with Chagas disease and permanent heart pacemaker implantation were matched by implantation diagnosis with 52 individuals that required pacemaker, but without Chagas disease. The presence of antibodies that recognized the m2MACh was assessed in the two groups by ELISA and Western blot by using two peptide sequences of the (m2MAChR), the second extracellular domain (2e) and the third intracellular domain (3i).
Results. Serological response frequency against 2e-m2MAChR in Chagas patients was 32.7% compared with 3.8% (p<0.01) in the controls; response against 3i-m2MAChR was 51.9% compared with 19.2% (p<0.01) for the controls. No clinical differences were observed between individuals that presented anti-m2MAChR and those who did not.
Conclusion. The frequency of anti-m2MAChR was higher in patients with Chagas disease for two of the receptor domains. Furthermore, patients with pacemaker therapy are more likely to have anti-m2MAChR and infection by Trypanosoma cruzi. The anti-m2MAChR response is not associated with any discernable clinical manifestation in this group of patients.
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References
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8. Borda LE, Gorelik G, Genaro A, Goin JC, Borda ES. Human chagasic IgG interacting with lymphocyte neurotransmitter receptor triggers intracellular signal transduction. FASED J. 1990;4:1661-7.
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12. Retondaro FC, dos Santos Costa PC, Pedrosa RC, Kurtenbach E. Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients. FASEB J. 1999:13;2015-20.
13. Ribeiro AL, Giménez LE, Hernández CC, de Carvalho AC, Teixeira MM, Guedes VC, et al. Early occurrence of anti-muscarinic autoantibodies and abnormal vagal modulation in Chagas disease. Inter J Cardiol. 2007; 117:59-63.
14. Baba A, Yoshikawa T, Fukuda Y, Sugiyama T, Shimada M, Akaishi M, et al. Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy. Eur Heart J. 2004;25:1108-15.
15. Del Corsso C, Carvalho AC, Martino HF, Varanda WA. Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in cardiomyocytes isolated from rabbits. Am J Physiol Heart Circ Physiol. 2004;287:H1928-36.
16. Hernández CC, Barcellos LC, Giménez LE, Cabarcas RA, García S, Pedrosa RC, et al. Human chagasic IgGs bind to cardiac muscarinic receptors and impair L-type Ca2+ currents. Cardiovasc Res. 2003;58:55-65.
17. Ribeiro AL, Giménez LE, Hernández CC, de Carvalho AC, Teixeira MM, Guedes VC, et al. Early occurrence of anti-muscarinic autoantibodies and abnormal vagal modulation in Chagas disease. Int J Cardiol. 2007; 117:59-63.
18. Corrêa MB, Pedrosa RC, Pereira BB, Corrêa WB, Medeiros A, Costa PC. Chronic Chagas disease patients with sinus node dysfunction: is the presence of IgG antibodies with muscarinic agonist action independent of left ventricular dysfunction. Rev Soc Bras Med Trop. 2007;40:665-71.
19. Medei E, Pedrosa RC, Benchimol PR, Costa PC, Hernández CC, Chaves EA, et al. Human antibodies with muscarinic activity modulate ventricular repolarization: basis for electrical disturbance. Int J Cardiol. 2007;115:373-80.
20. Talvani A, Rocha MO, Ribeiro AL, Borda E, Sterin-Borda L, Teixeira MM. Levels of anti-M2 and anti-beta1 autoantibodies do not correlate with the degree of heart dysfunction in Chagas’ heart disease. Microbes Infect. 2006;8:2459-64.
21. Mora G, Echeverry M, Rey G, López M, Posada L, Rivas F. Frecuencia de anticuerpos anti-Trypanosoma cruzi en pacientes portadores de marcapasos de la Clínica San Pedro Claver de Bogotá. Biomédica. 2007;27:483-9.
22. Luetje C, Brumwel C, Gainer M, Peterson G, Schimerlik M, Nathanson N. Isolation and characterization of monoclonal antibodies specific for the cardiac muscarinic acetylcholine receptor. Biochemestry. 1987;26:6892-6.
23. Cremaschi G, Fernández MM, Gorelik G, Goin JC, Fossati CA, Zwirner NW, et al. Modulatory effects on myocardial physiology induced by an anti-Trypanosoma cruzi monoclonal antibody involve recognition of major antigenic epitopes from beta1-adrenergic and M2-muscarinic cholinergic receptors without requiring receptor cross-linking. J Neuroimmunol. 2004;153:99-107.
24. Masuda MO, Levin M, De Oliveira SF, Dos Santos PC, Bergami PL, Dos Santos NA, et al. Functionally active cardiac antibodies in chronic Chagas’ disease are specifically blocked by Trypanosoma cruzi antigens. FASEB J. 1998;12:1551-8.
25. Sterin-Borda L, Giordanengo L, Joensen L, Gea S. Cruzipain induces autoantibodies against cardiac muscarinic acetylcholine receptors. Functional and pathological implications. Eur J Immunol. 2003;33: 2459-68.
26. Fu ML. Characterization of anti-heart M2 muscarinic receptor antibodies -a combined clinical and experimental study. Mol Cell Biochem. 1996;163:343-7.
27. Retondaro FC, Dos Santos PC, Pedrosa RC, Kurtenbach E. Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients. FASEB J. 1999;13:2015-20.
28. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simões MV. Pathogenesis of chronic Chagas heart disease. Circulation. 2007;115:1109-23.
2. Myslivecek J, Nováková M, Palkovits M, Krizanová O, Kvetnanský R. Distribution of mRNA and binding sites of adrenoceptors and muscarinic receptors in the rat heart. Life Sci. 2006;79:112-20.
3. Wang H, Han H, Zhang L, Shi H, Schram G, Nattel S, et al. Expression of multiple subtypes of muscarinic receptors and cellular distribution in the human heart. Mol Pharmacol. 2001;59:1029-36.
4. Pierce KL, Lefkowitz RJ. Classical and new roles of beta-arrestins in the regulation of G-protein-coupled receptors. Nat Rev Neurosci. 2001;2:727-33.
5. Goin JC, Borda ES, Auger S, Storino R, Sterin L. Cardiac M2 muscarinic cholinoceptor activation by human autoantibodies: association with bradycardia. Heart. 1999;82:273-8.
6. Joensen L, Borda E, Kohout T, Perry S, García G, Sterin L. Trypanosoma cruzi antigen that interacts with the β1-adrenergic receptor and modifies myocardial contractile activity. Mol Biochem Parasitol. 2003;127:169-77.
7. Peter JC, Wallukat G, Tugler J, Maurice D, Roegel JC, Briand JP, et al. Modulation of the M2 muscarinic acetylcholine receptor activity with monoclonal anti-M2 receptor antibody fragments. J Biol Chem. 2004;279:55697-706.
8. Borda LE, Gorelik G, Genaro A, Goin JC, Borda ES. Human chagasic IgG interacting with lymphocyte neurotransmitter receptor triggers intracellular signal transduction. FASED J. 1990;4:1661-7.
9. Goin JC, Perez C, Borda E, Sterin BL. Interaction of human chagasic IgG with the second extracellular loop of the human heart muscarinic acetylholine receptor: functional and pathological implications. FASED J. 1997;10:77-83.
10. Goin JC, Borda E, Leiros CP, Storino R, Sterin-Borda L. Identification of antibodies with muscarinic cholinergic activity in human Chagas’ disease: Pathological implications. J Auton Nerv Syst. 1994;47:45-52.
11. Leiros C, Sterin-Borda L, Borda E, Goin JC, Hosey M. Desensitization and sequestration of human M2 mAChRs by autoantibodies from patients with Chagas´disease. J Biol Chem. 1997;272:12989-93.
12. Retondaro FC, dos Santos Costa PC, Pedrosa RC, Kurtenbach E. Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients. FASEB J. 1999:13;2015-20.
13. Ribeiro AL, Giménez LE, Hernández CC, de Carvalho AC, Teixeira MM, Guedes VC, et al. Early occurrence of anti-muscarinic autoantibodies and abnormal vagal modulation in Chagas disease. Inter J Cardiol. 2007; 117:59-63.
14. Baba A, Yoshikawa T, Fukuda Y, Sugiyama T, Shimada M, Akaishi M, et al. Autoantibodies against M2-muscarinic acetylcholine receptors: new upstream targets in atrial fibrillation in patients with dilated cardiomyopathy. Eur Heart J. 2004;25:1108-15.
15. Del Corsso C, Carvalho AC, Martino HF, Varanda WA. Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in cardiomyocytes isolated from rabbits. Am J Physiol Heart Circ Physiol. 2004;287:H1928-36.
16. Hernández CC, Barcellos LC, Giménez LE, Cabarcas RA, García S, Pedrosa RC, et al. Human chagasic IgGs bind to cardiac muscarinic receptors and impair L-type Ca2+ currents. Cardiovasc Res. 2003;58:55-65.
17. Ribeiro AL, Giménez LE, Hernández CC, de Carvalho AC, Teixeira MM, Guedes VC, et al. Early occurrence of anti-muscarinic autoantibodies and abnormal vagal modulation in Chagas disease. Int J Cardiol. 2007; 117:59-63.
18. Corrêa MB, Pedrosa RC, Pereira BB, Corrêa WB, Medeiros A, Costa PC. Chronic Chagas disease patients with sinus node dysfunction: is the presence of IgG antibodies with muscarinic agonist action independent of left ventricular dysfunction. Rev Soc Bras Med Trop. 2007;40:665-71.
19. Medei E, Pedrosa RC, Benchimol PR, Costa PC, Hernández CC, Chaves EA, et al. Human antibodies with muscarinic activity modulate ventricular repolarization: basis for electrical disturbance. Int J Cardiol. 2007;115:373-80.
20. Talvani A, Rocha MO, Ribeiro AL, Borda E, Sterin-Borda L, Teixeira MM. Levels of anti-M2 and anti-beta1 autoantibodies do not correlate with the degree of heart dysfunction in Chagas’ heart disease. Microbes Infect. 2006;8:2459-64.
21. Mora G, Echeverry M, Rey G, López M, Posada L, Rivas F. Frecuencia de anticuerpos anti-Trypanosoma cruzi en pacientes portadores de marcapasos de la Clínica San Pedro Claver de Bogotá. Biomédica. 2007;27:483-9.
22. Luetje C, Brumwel C, Gainer M, Peterson G, Schimerlik M, Nathanson N. Isolation and characterization of monoclonal antibodies specific for the cardiac muscarinic acetylcholine receptor. Biochemestry. 1987;26:6892-6.
23. Cremaschi G, Fernández MM, Gorelik G, Goin JC, Fossati CA, Zwirner NW, et al. Modulatory effects on myocardial physiology induced by an anti-Trypanosoma cruzi monoclonal antibody involve recognition of major antigenic epitopes from beta1-adrenergic and M2-muscarinic cholinergic receptors without requiring receptor cross-linking. J Neuroimmunol. 2004;153:99-107.
24. Masuda MO, Levin M, De Oliveira SF, Dos Santos PC, Bergami PL, Dos Santos NA, et al. Functionally active cardiac antibodies in chronic Chagas’ disease are specifically blocked by Trypanosoma cruzi antigens. FASEB J. 1998;12:1551-8.
25. Sterin-Borda L, Giordanengo L, Joensen L, Gea S. Cruzipain induces autoantibodies against cardiac muscarinic acetylcholine receptors. Functional and pathological implications. Eur J Immunol. 2003;33: 2459-68.
26. Fu ML. Characterization of anti-heart M2 muscarinic receptor antibodies -a combined clinical and experimental study. Mol Cell Biochem. 1996;163:343-7.
27. Retondaro FC, Dos Santos PC, Pedrosa RC, Kurtenbach E. Presence of antibodies against the third intracellular loop of the m2 muscarinic receptor in the sera of chronic chagasic patients. FASEB J. 1999;13:2015-20.
28. Marin-Neto JA, Cunha-Neto E, Maciel BC, Simões MV. Pathogenesis of chronic Chagas heart disease. Circulation. 2007;115:1109-23.
How to Cite
1.
Echeverry MC, Tovar NC, Mora G. Presence of antibodies to cardiac neuroreceptors in patients with Chagas disease. Biomed. [Internet]. 2009 Sep. 1 [cited 2025 Apr. 4];29(3):476-84. Available from: https://revistabiomedicaorg.biteca.online/index.php/biomedica/article/view/17
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