Luciana Gabriel Nogueira1, Amanda Farage Frade2, Barbara Maria Ianni3, Laurie Laugier4, Cristina Wide Pissetti5, Sandrine Cabantous6, Monique Baron7, Gisele de Lima Peixoto8, Ariana de Melo Borges9, Eduardo Donadi10, José A Marin-Neto11, André Schmidt12, Fabrício Dias13, Bruno Saba14, Hui-Tzu Lin Wang15, Abilio Fragata16, Marcelo Sampaio17, Mario Hiroyuki Hirata18, Paula Buck19, Charles Mady20, Martino Martinelli21, Mariana Lensi22, Sergio Freitas Siqueira23, Alexandre Costa Pereira24, Virmondes Rodrigues25, Jorge Kalil26, Christophe Chevillard27, Edecio Cunha-Neto28. 1. Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: luciananogueira@usp.br. 2. Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: affrade@yahoo.com.br. 3. Myocardiopathies Unit, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: barbara.ianni@incor.usp.br. 4. Aix-Marseille Université, INSERM, GIMP UMR_S906, 13385 Marseille, France. Electronic address: laugier.laurie@yahoo.fr. 5. Laboratory of Immunology, Universidade Federal do Triângulo Mineiro (UFTM), 40 Frei Paulino, 48036-180 Uberaba, MG, Brazil. Electronic address: cristinawpissetti@gmail.com. 6. Aix-Marseille Université, INSERM, GIMP UMR_S906, 13385 Marseille, France. Electronic address: sandrine.ambard@univ-amu.fr. 7. Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: moni.baron@hotmail.com. 8. Pacemaker Clinic, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: gisellepeixoto@ig.com.br. 9. Laboratory of Immunology, Universidade Federal do Triângulo Mineiro (UFTM), 40 Frei Paulino, 48036-180 Uberaba, MG, Brazil. Electronic address: ariana_borges@hotmail.com. 10. School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, São Paulo, Brazil. Electronic address: eadonadi@fmrp.usp.br. 11. School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, São Paulo, Brazil. Electronic address: jamneto@fmrp.usp.br. 12. School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, São Paulo, Brazil. Electronic address: aschmidt@fmrp.usp.br. 13. School of Medicine of Ribeirão Preto (FMRP), University of São Paulo, São Paulo, Brazil. Electronic address: diasfc@gmail.com. 14. Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: brunosaba@hotmail.com. 15. Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: lin.ht.wang@gmail.com. 16. Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: a.frag@terra.com.br. 17. Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: msampaio@cardiol.br. 18. Dante Pazzanese Institute of Cardiology and Heart Failure Unit, São Paulo, Brazil. Electronic address: mhhirata@usp.br. 19. Myocardiopathies Unit, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: paula.buck@uol.com.br. 20. Myocardiopathies Unit, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: charles.mady@incor.usp.br. 21. Pacemaker Clinic, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: martino.filho@incor.usp.br. 22. Pacemaker Clinic, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: marilensi@hotmail.com. 23. Pacemaker Clinic, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: siqueira@incor.usp.br. 24. Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: alexandre.pereira@incor.usp.br. 25. Laboratory of Immunology, Universidade Federal do Triângulo Mineiro (UFTM), 40 Frei Paulino, 48036-180 Uberaba, MG, Brazil. Electronic address: vrodrigues@mednet.com.br. 26. Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: jkalil@usp.br. 27. Aix-Marseille Université, INSERM, GIMP UMR_S906, 13385 Marseille, France. Electronic address: christophe.chevillard@univ-amu.fr. 28. Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil; Institute for Investigation in Immunology (iii), INCT, São Paulo, Brazil. Electronic address: edecunha@gmail.com.
Abstract
BACKGROUND: Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. METHODS AND RESULTS: We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathy patients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. CONCLUSIONS: Our analysis suggests that the IL18 rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.
BACKGROUND:Chronic Chagas Disease cardiomyopathy (CCC), a life-threatening inflammatory dilated cardiomyopathy, affects 30% of the approximately 8 million patients infected by Trypanosoma cruzi, the rest of the infected subjects remaining asymptomatic (ASY). The Th1 T cell-rich myocarditis plays a pivotal role in CCC pathogenesis. Local expression of IL-18 in CCC myocardial tissue has recently been described. IL-18 could potentially amplify the process by inducing increased expression of IFN-γ which in turn can increase the production of IL-18, thereby creating a positive feedback mechanism. In order to assess the contribution of the IL-18 to susceptibility to Chronic Chagas Disease, we investigated the association between a single nucleotide polymorphism (SNP) located in the IL-18 gene with the risk of developing Chagas cardiomyopathy. METHODS AND RESULTS: We analyzed the rs2043055 marker in the IL18 gene in a cohort of Chagas disease cardiomyopathypatients (n=849) and asymptomatic subjects (n=202). We found a significant difference in genotype frequencies among moderate and severe CCC patients with ventricular dysfunction. CONCLUSIONS: Our analysis suggests that the IL18rs2043055 polymorphism- or a SNP in tight linkage disequilibrium with it- may contribute to modulating the Chagas cardiomyopathy outcome.
Authors: Katherine Yih-Jia Fu; Roxana Zamudio; Jo Henderson-Frost; Alex Almuedo; Hannah Steinberg; Steven Joseph Clipman; Gustavo Duran; Rachel Marcus; Thomas Crawford; Daniel Alyesh; Rony Colanzi; Jorge Flores; Robert Hugh Gilman; Caryn Bern Journal: Rev Soc Bras Med Trop Date: 2017 Jul-Aug Impact factor: 1.581
Authors: Carlos-Henrique D Barbosa; Fábio B Canto; Ariel Gomes; Layza M Brandao; Jéssica R Lima; Guilherme A Melo; Alessandra Granato; Eula G A Neves; Walderez O Dutra; Ana-Carolina Oliveira; Alberto Nóbrega; Maria Bellio Journal: Elife Date: 2022-06-07 Impact factor: 8.713
Authors: Daniel A Leon Rodriguez; F David Carmona; Luis Eduardo Echeverría; Clara Isabel González; Javier Martin Journal: PLoS Negl Trop Dis Date: 2016-03-30
Authors: Nathalie de Sena Pereira; Tamyres Bernadete Dantas Queiroga; Daniela Ferreira Nunes; Cléber de Mesquita Andrade; Manuela Sales Lima Nascimento; Maria Adelaide Do-Valle-Matta; Antônia Cláudia Jácome da Câmara; Lúcia Maria da Cunha Galvão; Paulo Marcos Matta Guedes; Egler Chiari Journal: PLoS Negl Trop Dis Date: 2018-07-25