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Published on: July 29, 2012
Immunologic changes in the peripheral blood transcriptome of individuals with early-stage chronic Chagas
Carolina Duque1, Jaime So2, Yagahira E Castro-Sesquen3
1Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Insights
Early Chagas cardiomyopathy (CCC) involves reduced immune response and T cell activation, distinct from other heart conditions. These findings may offer early biomarkers for CCC progression and treatment strategies.
Area of Science:
- Cardiology
- Immunology
- Genetics
Background:
- Chagas disease affects millions globally, with 20-30% developing chronic Chagas cardiomyopathy (CCC).
- The progression to advanced heart failure in CCC is poorly understood.
- This study investigates early physiologic changes in CCC development.
Purpose of the Study:
- To explore the physiologic changes associated with early chronic Chagas cardiomyopathy (CCC).
- To identify potential biomarkers for early CCC detection and progression.
- To differentiate the pathogenesis of CCC from other cardiomyopathies.
Main Methods:
- RNA sequencing was used to analyze gene expression in peripheral blood.
- Study groups included patients with Chagas disease (with and without heart disease) and controls.
- Pathway analysis and immune cell deconvolution were employed.
Main Results:
- Early CCC is linked to downregulated peripheral immune response genes.
- Reduced antigen presentation and T cell activation were observed.
- These immune changes appear distinct from non-Chagas cardiomyopathies.
Conclusions:
- The immune response plays a crucial role in early CCC pathogenesis.
- Identified gene expression changes may serve as early CCC biomarkers.
- Findings can inform future research on CCC progression and treatment.
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.
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