Key result
CD4+ T-cells from patients with chronic Chagas cardiomyopathy carrying DERAA-DRB1 alleles recognize and react to host-derived peptides with sequence similarity to parasite proteins, leading to T-cell activation and proliferation.
Why the study?
Chagas disease can cause dilated cardiomyopathy driven by T-cell-mediated inflammation, and specific DERAA-bearing HLA-DRB1 alleles have been linked to this severe manifestation.
Cross-Sectional (n=10)
No
CD4+ T-cells from Chagas cardiomyopathy patients recognize self-peptides presented by DERAA-bearing HLA-DRB1 alleles, suggesting an autoimmune component in the amplification of cardiac pathology.
Supports autoimmune mechanisms in Chagas cardiomyopathy progression; hypothesis-generating and should not change practice without prospective studies.
Introduction: causes Chagas disease, which may lead to a deadly dilated cardiomyopathy resulting from T-cell-mediated inflammation. We found that specific HLA-DRB1 alleles (*0103, *0402, *1301, and *1302) that display the DERAA motif are linked to this severe clinical manifestation of Chagas disease. Methods: functional assays, and single-cell RNA sequencing to determine the response of CD4+ T cells from indeterminate (IND) and cardiac (CCC) Chagas patients to peptides selected on DERAA-bearing alleles. Results: We observed that these alleles display binding affinity towards host-derived peptides with sequence similarity to parasite-derived proteins. These peptides can activate and induce proliferation of CD4+ T-cells from CCC, but not IND. Importantly, the magnitude of this response correlated with the severity of ventricular dysfunction and increased production of soluble factors associated with myocardial fibrosis. Analysis of differentially expressed genes (DEGs) in activated CD4+ T-cells from individuals with the DERAA-DRB1 alleles demonstrated a high expression of cytotoxic, chemotactic and proapoptotic genes, linking these cells with pathogenic functions. Finally, we observed the upregulation of genes that code for the host proteins that contain the potentially pathogenic peptides in the cardiac tissue of CCC, suggesting their involvement in cardiomyopathy. Discussion: Our findings highlight the ability of CD4+ T-cells from CCC patients to recognize and react to foreign and self-peptides, thereby emphasizing the importance of HLA-DRB1 alleles in the presentation of potentially pathogenic antigens and in the amplification of CCC pathology.
No takes yet. Share an insight, caveat, or question.
Silva et al. (2025) conducted a cross-sectional in Chagas disease (Indeterminate and Chronic Chagas Cardiomyopathy) (n=10). Self and parasite-derived peptides selected upon DERAA-bearing HLA-DRB1 alleles vs. Media plus anti-CD28 (unstimulated control) was evaluated on CD4+ T-cell activation and proliferation (CD69 expression in blast cells). CD4+ T-cells from patients with chronic Chagas cardiomyopathy carrying DERAA-DRB1 alleles recognize and react to host-derived peptides with sequence similarity to parasite proteins, leading to T-cell activation and proliferation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: