Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional studyResearch in context
Summary: Background: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected disease that affects approximately 6 million individuals worldwide. Of those infected, 20–30% will go on to develop chronic Chagas cardiomyopathy (CCC), and many ultimately to advanced heart fail...
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Elsevier
2025-05-01
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| Series: | The Lancet Regional Health. Americas |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667193X25001000 |
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| author | Carolina Duque Jaime So Yagahira E. Castro-Sesquen Kelly DeToy Sneider A. Gutierrez Guarnizo Fatemeh Jahanbakhsh Edith Malaga Machaca Monica Miranda-Schaeubinger Indira Chakravarti Virginia Cooper Mary E. Schmidt Luigi Adamo Rachel Marcus Kawsar R. Talaat Robert H. Gilman Monica R. Mugnier |
| author_facet | Carolina Duque Jaime So Yagahira E. Castro-Sesquen Kelly DeToy Sneider A. Gutierrez Guarnizo Fatemeh Jahanbakhsh Edith Malaga Machaca Monica Miranda-Schaeubinger Indira Chakravarti Virginia Cooper Mary E. Schmidt Luigi Adamo Rachel Marcus Kawsar R. Talaat Robert H. Gilman Monica R. Mugnier |
| author_sort | Carolina Duque |
| collection | DOAJ |
| description | Summary: Background: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected disease that affects approximately 6 million individuals worldwide. Of those infected, 20–30% will go on to develop chronic Chagas cardiomyopathy (CCC), and many ultimately to advanced heart failure. The mechanisms by which this progression occurs are poorly understood. In this exploratory study, we sought to provide insight into the physiologic changes associated with the development of early CCC. Methods: We used RNA sequencing to analyse the gene expression changes in the peripheral blood of six patients with Chagas disease with early structural heart disease, four patients with Chagas disease without any signs or symptoms of disease, thirteen patients without Chagas disease with early structural heart disease, and ten patients without Chagas disease or signs of heart disease. Pathway analyses and immune cell deconvolution were employed to further elucidate the biological processes underlying early CCC development. Findings: Our analysis suggests that early CCC is associated with a downregulation of various peripheral immune response genes, including changes suggestive of reduced antigen presentation and T cell activation. Notably, these genes and processes appear to be distinct from those of non-Chagas cardiomyopathies. Interpretation: This work highlights the potential importance of the immune response in early CCC, providing insight into the early pathogenesis of this disease and how it may differ from other cardiomyopathies. The changes we have identified may serve as biomarkers of early CCC and could inform future longitudinal cohort studies of markers of disease progression and strategies for the treatment of CCC in its early stages. Funding: NIH, FONDECYT, IDSA, NSF. |
| format | Article |
| id | doaj-art-d1d4dfe4c00e4d73b8ae5679e721c693 |
| institution | OA Journals |
| issn | 2667-193X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | The Lancet Regional Health. Americas |
| spelling | doaj-art-d1d4dfe4c00e4d73b8ae5679e721c6932025-08-20T02:28:07ZengElsevierThe Lancet Regional Health. Americas2667-193X2025-05-014510109010.1016/j.lana.2025.101090Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional studyResearch in contextCarolina Duque0Jaime So1Yagahira E. Castro-Sesquen2Kelly DeToy3Sneider A. Gutierrez Guarnizo4Fatemeh Jahanbakhsh5Edith Malaga Machaca6Monica Miranda-Schaeubinger7Indira Chakravarti8Virginia Cooper9Mary E. Schmidt10Luigi Adamo11Rachel Marcus12Kawsar R. Talaat13Robert H. Gilman14Monica R. Mugnier15Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USADepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USAMedStar Washington Hospital Center, Washington, D.C., USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USADepartment of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Corresponding author.Summary: Background: Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a neglected disease that affects approximately 6 million individuals worldwide. Of those infected, 20–30% will go on to develop chronic Chagas cardiomyopathy (CCC), and many ultimately to advanced heart failure. The mechanisms by which this progression occurs are poorly understood. In this exploratory study, we sought to provide insight into the physiologic changes associated with the development of early CCC. Methods: We used RNA sequencing to analyse the gene expression changes in the peripheral blood of six patients with Chagas disease with early structural heart disease, four patients with Chagas disease without any signs or symptoms of disease, thirteen patients without Chagas disease with early structural heart disease, and ten patients without Chagas disease or signs of heart disease. Pathway analyses and immune cell deconvolution were employed to further elucidate the biological processes underlying early CCC development. Findings: Our analysis suggests that early CCC is associated with a downregulation of various peripheral immune response genes, including changes suggestive of reduced antigen presentation and T cell activation. Notably, these genes and processes appear to be distinct from those of non-Chagas cardiomyopathies. Interpretation: This work highlights the potential importance of the immune response in early CCC, providing insight into the early pathogenesis of this disease and how it may differ from other cardiomyopathies. The changes we have identified may serve as biomarkers of early CCC and could inform future longitudinal cohort studies of markers of disease progression and strategies for the treatment of CCC in its early stages. Funding: NIH, FONDECYT, IDSA, NSF.http://www.sciencedirect.com/science/article/pii/S2667193X25001000ChagasCardiomyopathyGene expressionImmuneBiomarkers |
| spellingShingle | Carolina Duque Jaime So Yagahira E. Castro-Sesquen Kelly DeToy Sneider A. Gutierrez Guarnizo Fatemeh Jahanbakhsh Edith Malaga Machaca Monica Miranda-Schaeubinger Indira Chakravarti Virginia Cooper Mary E. Schmidt Luigi Adamo Rachel Marcus Kawsar R. Talaat Robert H. Gilman Monica R. Mugnier Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional studyResearch in context The Lancet Regional Health. Americas Chagas Cardiomyopathy Gene expression Immune Biomarkers |
| title | Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional studyResearch in context |
| title_full | Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional studyResearch in context |
| title_fullStr | Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional studyResearch in context |
| title_full_unstemmed | Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional studyResearch in context |
| title_short | Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas cardiomyopathy: a cross-sectional studyResearch in context |
| title_sort | immunologic changes in the peripheral blood transcriptome of individuals with early stage chronic chagas cardiomyopathy a cross sectional studyresearch in context |
| topic | Chagas Cardiomyopathy Gene expression Immune Biomarkers |
| url | http://www.sciencedirect.com/science/article/pii/S2667193X25001000 |
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