Correlation of blood-based immune molecules with cardiac gene expression profiles reveals insights into Chagas cardiomyopathy pathogenesis

Abstract

IntroductionUnderstanding compartmentalized immune responses in target organs is crucial for elucidating the pathogenesis of various diseases. However, obtaining samples from affected vital organs often poses safety challenges. In this study, we aimed to investigate potential correlations between the levels of disease-associated immune molecules in the bloodstream with their gene expression profiles in the hearts of patients suffering from Chagas Cardiomyopathy (CCC). This debilitating and often fatal condition is caused by infection with the protozoan Trypanosoma cruzi.MethodsBlood samples were analyzed using the Bio-Plex platform. Gene Expression Omnibus (GEO) database was used to determine gene expression profile in heart tissue from CCC and non-Chagas controls (CTRL).ResultsElevated levels of inflammatory cytokines were detected in the plasma of CCC patients, and these levels correlated with clinical indicators of deteriorating cardiac function. Notably, 75% of the soluble factors assessed in the plasma exhibited a consistent relationship with their gene expression levels in the cardiac tissue of CCC patients. Analysis of interactions and signaling pathways related to these molecules revealed an overrepresentation of inflammatory pathways in both blood and heart compartments. Moreover, we identified that differentially expressed genes in CCC cardiac tissue were primarily associated with T-cell signaling pathways and correlated with the presence of CD8+ T cells in the myocardium.DiscussionOur findings establish a strong correlation between relevant immune molecules and their signaling pathways in both the blood and heart tissue in CCC. This validates the use of blood as a non-invasive medium for understanding immunopathology and identifying markers for cardiac dysfunction in Chagas disease.

Signatures of CD4+ T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy

“…Other phenotypic changes included an increase of Th17 and a decrease of Th1-like Tfh cells in asymptomatic patients but not in those with CCC. On the other hand, other studies show decrease in levels of IL-17 and proportions of IL-17 producing CD4 + T cells in CCC compared to asymptomatic patients and CTL (31,49). Although these findings are controversial, distinct Tfh phenotypes might contribute differently to Chagas disease progression (21,22).…”

“…Therefore, the association between circulating T helper cells and B cell subsets and CCC clinical form deserve further investigation. Notably, recent study established a positive correlation between immune molecules detected in the blood and in heart tissue in patients with Chagas disease ( 31 ). Hence, we created two high-dimensional flow cytometry panels to phenotype CD4 + T and B cells from patients with distinct clinical phases of chronic Chagas disease.…”