Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil

Author:

Sunderraj Ashwin1,Cunha Luisa Marin2,Avila Matheus2,Alexandria Shaina3,Ferreira Ariela Mota4ORCID,de Oliveira-da Silva Léa Campos5,Ribeiro Antonio L. P.6ORCID,Nunes Maria do Carmo Pereira6,Sabino Ester C.5ORCID,Landay Alan7,Kalil Jorge8ORCID,Chevillard Christophe9ORCID,Cunha-Neto Edecio8ORCID,Feinstein Matthew J.10

Affiliation:

1. Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA

2. Faculdade de Ciências Médicas de Santos, UNILUS, Santos 11045-101, Brazil

3. Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA

4. Graduate Program in Health Sciences, State University of Montes Claros, Montes Claros 39401-089, Brazil

5. Institute of Tropical Medicine, University of São Paulo, São Paulo 05403-000, Brazil

6. Department of Internal Medicine, Federal University of Minas Gerais, Belo Horizonte 31270-901, Brazil

7. Division of Geriatrics and Gerontology, Department of Medicine, Rush University Medical Center, Chicago, IL 60612, USA

8. Laboratory of Immunology, Heart Institute Instituto do Coração (InCor), School of Medicine, University of São Paulo, São Paulo 05403-000, Brazil

9. Institut MarMaRa, TAGC Theories and Approaches of Genomic Complexity, Aix Marseille Université, 13385 Marseille, France

10. Division of Cardiology, Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA

Abstract

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study.

Funder

Northwestern University Havey Institute for Global Health, global health catalyst grant project

Institut National de la Santé et de la Recherche Médicale

Aix-Marseille University

French Agency for Research

Inserm Cross-Cutting Project GOLD

Excellence Initiative of Aix-Marseille University

CAPES-COFECUB

NIH

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Cited by 1 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3