PMID- 33193300 OWN - NLM STAT- MEDLINE DCOM- 20210429 LR - 20210429 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - A Specific IL6 Polymorphic Genotype Modulates the Risk of Trypanosoma cruzi Parasitemia While IL18, IL17A, and IL1B Variant Profiles and HIV Infection Protect Against Cardiomyopathy in Chagas Disease. PG - 521409 LID - 10.3389/fimmu.2020.521409 [doi] LID - 521409 AB - BACKGROUND: Chagas disease caused by Trypanosoma cruzi (T. cruzi) affects approximately six million individuals worldwide. Clinical manifestations are expected to occur due to the parasite persistence and host immune response. Herein we investigated potential associations between IL1B, IL6, IL17A, or IL18 polymorphism profiles and cardiomyopathy or T. cruzi parasitemia, as well as the impact of HIV infection on cardiopathy. METHODS: Two hundred twenty-six patients and 90 control individuals were analyzed. IL1B rs1143627 T>C, IL6 rs1800795 C>G, IL17A rs2275913 G>A, IL18 rs187238 C>G, and IL18 rs1946518 C>A SNVs were analyzed by real-time PCR and T. cruzi parasitemia by PCR. RESULTS: Our data revealed association between a cytokine gene polymorphism and parasitemia never previously reported. The IL6 rs1800795 CG genotype lowered the risk of positive parasitemia (OR = 0.45, 95% CI 0.24-0.86, P = 0.015). Original findings included associations between IL17A rs2275913 AA and IL18 s1946518 AA genotypes with decreased risk of developing cardiomyopathy (OR = 0.27, 95% CI 0.07-0.97, P = 0.044; and OR = 0.35, 95% CI 0.14-0.87, P = 0.023, respectively). IL18 rs1946518 AA and IL1B rs1143627 TC were associated with reduced risk for cardiomyopathy severity, including NYHA (New York Heart Association) class >/= 2 (OR = 0.21, 95% CI 0.06-0.68, P = 0.009; and OR = 0.48, 95% CI 0.24-0.95, P = 0.036, respectively) and LVEF (left ventricular ejection fraction) <45% for IL18 rs1946518 AA (OR = 0.22, 95% CI 0.05-0.89, P = 0.034). A novel, unexpected protective effect of HIV infection against development/progression of cardiomyopathy was identified, based on a lower risk of developing cardiopathy (OR = 0.48, 95% CI 0.23-0.96, P = 0.039), NYHA class >/= 2 (OR = 0.15, 95% CI 0.06-0.39, P < 0.001), and LVEF < 45% (OR = 0.03, 95% CI 0.00-0.25, P = 0.001). Digestive involvement was negatively associated with NYHA >/= 2 and LVEF < 45% (OR = 0.20, 95% CI 0.09-0.47, P < 0.001; and OR = 0.24, 95% CI 0.09-0.62, P = 0.004, respectively). CONCLUSIONS: Our data support a protective role of IL17A AA, IL18 AA, and IL1B TC genotypes against development/progression of cardiomyopathy and a modulatory effect of the IL6 CG genotype on the risk of parasitemia in Chagas disease. Notably, HIV infection was shown to protect against development/progression of cardiopathy, potentially associated with a synergistic effect of HIV and highly active antiretroviral therapy (HAART), attenuating a Th1-mediated response in the myocardium. This proposed hypothesis requires confirmation, however, in larger and more comprehensive future studies. CI - Copyright (c) 2020 Gomes dos Santos, Watanabe, Ferreira, Oliveira, Nakanishi, Oliveira, Bocchi, Novaes, Cruz, Carvalho, Sato, Yamashiro-Kanashiro, Pontillo, de Freitas, Onuchic and Shikanai-Yasuda. FAU - Gomes Dos Santos, Alexandra AU - Gomes Dos Santos A AD - Department of Infectious and Parasitic Diseases, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Watanabe, Elieser Hitoshi AU - Watanabe EH AD - Department of Medicine, Divisions of Molecular Medicine and Nephrology, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Ferreira, Daiane Tomomi AU - Ferreira DT AD - Laboratory of Immunology (LIM 48), Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Oliveira, Jamille AU - Oliveira J AD - Department of Infectious and Parasitic Diseases, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Nakanishi, Erika Shimoda AU - Nakanishi ES AD - Laboratory of Immunology (LIM 48), Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Oliveira, Claudia Silva AU - Oliveira CS AD - Department of Infectious and Parasitic Diseases, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Bocchi, Edimar AU - Bocchi E AD - Heart Institute, Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Novaes, Cristina Terra Gallafrio AU - Novaes CTG AD - Division of Infectious Diseases, Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Cruz, Fatima AU - Cruz F AD - Heart Institute, Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Carvalho, Noemia Barbosa AU - Carvalho NB AD - Division of Infectious Diseases, Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Sato, Paula Keiko AU - Sato PK AD - Laboratory of Immunology (LIM 48), Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Yamashiro-Kanashiro, Edite Hatsumi AU - Yamashiro-Kanashiro EH AD - Laboratory of Immunology (LIM 48), Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. AD - Instituto de Medicina Tropical, University of Sao Paulo, Sao Paulo, Brazil. FAU - Pontillo, Alessandra AU - Pontillo A AD - Departament of Immunology, Instituto de Ciencias Biomedicas (ICB), University of Sao Paulo, Sao Paulo, Brazil. FAU - de Freitas, Vera Lucia Teixeira AU - de Freitas VLT AD - Department of Infectious and Parasitic Diseases, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. AD - Laboratory of Immunology (LIM 48), Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Onuchic, Luiz Fernando AU - Onuchic LF AD - Department of Medicine, Divisions of Molecular Medicine and Nephrology, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. FAU - Shikanai-Yasuda, Maria Aparecida AU - Shikanai-Yasuda MA AD - Department of Infectious and Parasitic Diseases, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. AD - Laboratory of Immunology (LIM 48), Hospital das Clinicas, Faculdade de Medicina, University of Sao Paulo, Sao Paulo, Brazil. LA - eng SI - Dryad/10.5061/dryad.wstqjq2hn PT - Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201022 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (IL17A protein, human) RN - 0 (IL18 protein, human) RN - 0 (IL1B protein, human) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-17) RN - 0 (Interleukin-18) RN - 0 (Interleukin-1beta) RN - 0 (Interleukin-6) SB - IM MH - Adult MH - *Chagas Disease/genetics/immunology MH - Female MH - *Genotype MH - Humans MH - *Interleukin-17/genetics/immunology MH - *Interleukin-18/genetics/immunology MH - *Interleukin-1beta/genetics/immunology MH - *Interleukin-6/genetics/immunology MH - Male MH - Middle Aged MH - *Parasitemia/genetics/immunology MH - *Polymorphism, Genetic MH - Trypanosoma cruzi/*immunology PMC - PMC7642879 OTO - NOTNLM OT - Chagas disease OT - HIV OT - IL1 B OT - IL17 A and IL18 polymorphisms OT - IL6 OT - T. cruzi parasitemia OT - cardiomyopathy EDAT- 2020/11/17 06:00 MHDA- 2021/04/30 06:00 PMCR- 2020/01/01 CRDT- 2020/11/16 08:47 PHST- 2019/12/18 00:00 [received] PHST- 2020/09/24 00:00 [accepted] PHST- 2020/11/16 08:47 [entrez] PHST- 2020/11/17 06:00 [pubmed] PHST- 2021/04/30 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.521409 [doi] PST - epublish SO - Front Immunol. 2020 Oct 22;11:521409. doi: 10.3389/fimmu.2020.521409. eCollection 2020.