Abstract
Background
Studies indicate that antibodies cross-reacting with cardiac β1 adrenergic receptors
are likely to play a role in the development of chronic Chagas heart disease (CCHD).
In parallel, clinical trials have shown that β1 antagonist drugs exert beneficial
effects in the prognosis of patients with CCHD. In a group of patients with CCHD undergoing
therapy with β1-blockers, we have now evaluated the levels of anti-p2β antibodies
and the severity of CCHD.
Methods
We performed a cross-sectional study in Trypanosoma cruzi seropositive patients categorized according to a standard CCHD classification. All
individuals were subjected to a complete clinical examination.
Results
There was no association between CCHD stages, electrocardiographic conduction disturbances,
and echocardiogram pathological signs with the levels of autoantibodies. However,
when patients were analyzed according to selective cardio-β1-blocker therapy, those
receiving treatment had higher levels of anti-p2β. Patients from CCHD stage III treated
with combined therapy of cardio-β1-selective blockers, enalapril, and statins, presented
decreased cardiac involvement and lower score of risk of mortality than individuals
from the same group who were not treated.
Conclusions
Our results suggest that selective cardio-β1-blockers might modify the autoantibody
anti-p2β levels, and that combined therapy in patients with stage III CCHD might be
associated with lower cardiac involvement and risk score of mortality in patients
with heart failure. Longitudinal studies will help to ascertain the proper role of
β1-blockers in the immunopathological processes underlying chronic Chagas disease.
Résumé
Introduction
Les études indiquent que les anticorps ayant une réaction croisée avec les récepteurs
β1-adrénergiques cardiaques sont susceptibles de jouer un rôle dans le développement
de la cardiopathie chagasique chronique (CCC). Parallèlement, les essais cliniques
ont montré que les antagonistes β1 exercent des effets bénéfiques dans le pronostic
des patients ayant une CCC. Dans un groupe de patients ayant une CCC subissant le
traitement par des β1-bloquants, nous avons maintenant évalué les concentrations d'anticorps
anti-p2β et la gravité de la CCC.
Méthodes
Nous avons réalisé une étude transversale chez des patients séropositifs pour le Trypanosoma cruzi répartis selon une classification standard de la CCC. Tous les individus étaient
sujets à un examen clinique complet.
Résultats
Il n'y avait aucune association entre les stades de la CCC, les perturbations de la
conduction électrocardiographique et les signes pathologiques à l'échocardiogramme
quant aux concentrations d'autoanticorps. Cependant, lorsque les patients étaient
analysés selon le traitement par β1-bloquants cardiosélectifs, ceux recevant le traitement
avaient des concentrations plus élevées d'anti-p2β. Les patients ayant une CCC de
stade III, qui reçoivent le traitement combiné de β1-bloquants cardiosélectifs, d'énalapril
et de statines, montraient une diminution de l'implication cardiaque et un plus faible
score de risque de mortalité que les individus du même groupe qui n'étaient pas traités.
Conclusions
Nos résultats suggèrent que les β1-bloquants cardiosélectifs pourraient modifier les
concentrations d'anticorps anti-p2β et que le traitement combiné chez les patients
ayant une CCC de stade III pourrait être associé à une implication cardiaque et un
score de risque de mortalité plus faibles chez les patients ayant une insuffisance
cardiaque. Des études longitudinales aideront à établir le rôle propre des β1-bloquants
dans les processus immunopathologiques de la maladie de Chagas chronique sous-jacente.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Control of Chagas disease: second report of a WHO expert committee.World Health Organ Tech Rep Ser. 2002; 905: 1-109
- Estimación cuantitativa de la enfermedad de Chagas en las Américas [Quantitative estimate of Chagas disease in the Americas].OMS, Montevideo, Uruguay2006 ([in Spanish])
- Update on Chagas heart disease on the first centenary of its discovery.Rev Esp Cardiol. 2009; 62: 1211-1216
- Determining the C-reactive protein level in patients with different clinical forms of Chagas disease.Rev Esp Cardiol. 2010; 63: 1096-1099
- Nuclear changes in cells parasitized by Trypanosoma cruzi in chronic Chagas disease patients.Rev Soc Bras Med Trop. 1987; 20: 147-151
- Denervation and heart disease in patients with chronic Chagas' disease.Arq Bras Cardiol. 1987; 48: 43-47
- Etiology of Chagas disease myocarditis: autoimmunity, parasite persistence, or both?.Trends Parasitol. 2003; 19: 19-22
- Autoimmunity in Chagas disease cardiomyopathy: fulfilling the criteria at last?.Parasitol Today. 1996; 12: 396-399
- Autoimmunity in Chagas heart disease.Int J Parasitol. 2001; 31: 555-561
- Immunological control of Trypanosoma cruzi infection and pathogenesis of Chagas disease.Int Arch Allergy Immunol. 1997; 114: 103-110
- The role of active myocarditis in the development of heart failure in chronic Chagas disease: a study based on endomyocardial biopsies.Clin Cardiol. 1987; 10: 665-670
- Experimental chronic Chagas disease myocarditis is an autoimmune disease preventable by induction of immunological tolerance to myocardial antigens.J Autoimmun. 2002; 18: 131-138
- The pathogenesis of Chagas disease: when autoimmune and parasite-specific immune responses meet.An Acad Bras Cienc. 2001; 73: 547-559
- Chagas disease: a new worldwide challenge.Nature. 2010; 465: S6-S7
- Chagas disease: 100 years after its discovery. A systemic review.Acta Trop. 2010; 115: 5-13
- Autoimmunity.Adv Parasitol. 2011; 76: 129-152
- Modulatory effects on myocardial physiology induced by an anti-monoclonal antibody involve recognition of major antigenic epitopes from β-adrenergic and M-muscarinic cholinergic receptors without requiring receptor cross-linking.J Neuroimmunol. 2004; 153: 99-107
- Trypanosoma cruzi antigen that interacts with the β1-adrenergic receptor and modifies myocardial contractile activity.Mol Biochem Parasitol. 2003; 127: 169-177
- Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.J Exp Med. 1995; 182: 59-65
- Anti-beta1-adrenergic receptor autoantibodies in patients with chronic Chagas heart disease.Clin Exp Immunol. 2007; 148: 440-449
- Human recombinant antibodies against Trypanosoma cruzi ribosomal P2 β protein.Parasitology. 2011; : 1-12
- Antibodies against the Trypanosoma cruzi ribosomal P proteins induce apoptosis in HL-1 cardiac cells.Int J Parasitol. 2011; 41: 635-644
- Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits.J Mol Cell Cardiol. 1997; 29: 641-655
- Antibodies against the carboxyl-terminal end of the Trypanosoma cruzi ribosomal P proteins are pathogenic.FASEB J. 2001; 15: 2602-2612
- Structural and functional analysis of the B cell epitopes recognized by anti-receptor autoantibodies in patients with Chagas disease.J Immunol. 1996; 157: 4203-4211
- Effects of β-blockers on outcome of patients with Chagas cardiomyopathy with chronic heart failure.Int J Cardiol. 2011; 151: 205-208
- β-Blocker therapy and mortality of patients with Chagas cardiomyopathy: a subanalysis of the REMADHE prospective trial.Circ Heart Fail. 2010; 3: 82-88
- CHARITY: Chagas cardiomyopathy bisoprolol intervention study: a randomized double-blind placebo force-titration controlled study with bisoprolol in patients with chronic heart failure secondary to Chagas cardiomyopathy [NCT00323973].Trials. 2006; 7: 21
Marcipar S, Lagier C. Advances in serological diagnosis of Chagas' disease by using recombinant proteins. In: Rodriguez-Morales A, ed. Current Topics in Tropical Medicine. Available at: http://www.intechopen.com/books/current-topics-in-tropicalmedicine/advances-in-serological-diagnosis-of-chagas-disease-by-using-recombinant-proteins. Accessed March 7, 2013.
- Clasificación clínica de la miocardiopatía chagásica crónica e historia natural [Clinical classification and natural evolution of chronic Chagas cardiomyopathy].Bol Acad Nac de Medicina (Bs As). 1985; 63 ([in Spanish]): 160
- ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC.Eur Heart J. 2012; 33: 1787-1847
- Development and validation of a risk score for predicting death in Chagas' heart disease.N Engl J Med. 2006; 355: 799-808
- Risk stratification in Chagas disease.Rev Esp Cardiol (Engl Ed). 2012; 65: 17-21
- Use of full-length recombinant calflagin and its c fragment for improvement of diagnosis of Trypanosoma cruzi infection.J Clin Microbiol. 2005; 43: 5498-5503
- Comparison of recombinant Trypanosoma cruzi peptide mixtures versus multiepitope chimeric proteins as sensitizing antigens for immunodiagnosis.Clin Vaccine Immunol. 2009; 16: 899-905
Tijssen, P. Processing of data and reporting of results of enzyme immunoassays. In: Practice and Theory of Enzyme Immunoassays. Laboratory Techniques in Biochemistry and Molecular Biology, Vol. 15. Amsterdam, London, New York, Tokyo: Elsevier, 1985:385-421.
- Standardisation and validation of enzyme-linked immunosorbent assay techniques for the detection of antibody in infectious disease diagnosis.Rev Sci Tech. 1993; 12: 435-450
- Design, construction, and evaluation of a specific chimeric antigen to diagnose chagasic infection.J Clin Microbiol. 2006; 44: 3768-3774
- Echocardiography in Chagas heart disease.Circulation. 2007; 115: 1124-1131
- 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: 2459-2464
- Integrate study of a Bolivian population infected by Trypanosoma cruzi, the agent of Chagas disease.Mem Inst Oswaldo Cruz. 2002; 97: 289-295
- Assessment of cross-reactive host-pathogen antibodies in patients with different stages of chronic Chagas disease.Rev Esp Cardiol. 2013; 66: 791-796
- Matrix metalloproteinases 2 and 9 as diagnostic markers in the progression to Chagas cardiomyopathy.Am Heart J. 2013; 165: 558-566
- Humoral immune response against P2β from Trypanosoma cruzi in persons with chronic Chagas disease: its relationship with treatment against parasites and myocardial damage.Am J Trop Med Hyg. 2011; 84: 575-580
- The BENEFIT trial: testing the hypothesis that trypanocidal therapy is beneficial for patients with chronic Chagas heart disease.Mem Inst Oswaldo Cruz. 2009; 104: 319-324
- Beneficial effects of enalapril on the diastolic ventricular function in Chagas myocardiopathy.Arq Bras Cardiol. 1993; 60: 273-278
- A randomized trial of carvedilol after renin-angiotensin system inhibition in chronic Chagas cardiomyopathy.Am Heart J. 2007; 153 (544.e1-8)
Article info
Publication history
Published online: December 26, 2013
Accepted:
September 18,
2013
Received:
July 20,
2013
Footnotes
See editorial by McLean and Oudit, pages 267-269 of this issue.
See page 336 for disclosure information.
Identification
Copyright
© 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
