Análise comparativa dos níveis plasmáticos de citocinas, quimiocinas, fatores de crescimento e subpopulações de linfócitos T entre a cardiopatia chagásica e cardiopatias de outras etiologias

Abstract

Chronic Chagas cardiomyopathy, an inflammatory heart disease, results from infection by the intracellular protozoan Trypanosoma cruzi. The immune response plays a pivotal role in the progression and pathogenesis of the disease through the release of inflammatory mediators in both systemic and tissue environments, contributing to cardiac tissue damage. The expression of cytokines, chemokines, and growth factors in patients with Chagas cardiomyopathy demonstrates a consistent association with a predominantly inflammatory immune profile. However, it remains unclear whether these mechanisms are exclusive to T. cruzi infection or if they are also present in heart diseases of other etiologies. Therefore, we aimed to investigate whether the immunological changes observed in patients with Chagas cardiomyopathy could also be identified in patients with heart diseases of other etiologies. The hypothesis of this study is that there are differences in the plasma levels of cytokines, chemokines, growth factors, and in the frequency of T cell subpopulations in samples from individuals with Chagas cardiomyopathy compared to those with idiopathic cardiomyopathy, of unknown cause, and rheumatic heart disease, of infectious etiology associated with Streptococcus group A. To address this, we quantified soluble mediators (cytokines, chemokines, and growth factors) in the plasma of individuals from different groups. In addition, the frequency of distinct T cell subpopulations was assessed by flow cytometry. Our findings demonstrated that the plasma levels of most of the soluble mediators evaluated were significantly elevated in Chagas cardiomyopathy compared to the other heart diseases and the control group, indicating a strong immune activation in this group. On the other hand, some similarities were evidenced by increased plasma levels of mediators shared across different heart diseases. Notably, IL-1Ra levels were higher in all groups when compared to controls. Moreover, the levels of IFN-γ, IL-4, IL-17, the chemokine CCL4, and the growth factor PDGF-BB were elevated in both Chagas and rheumatic heart diseases. The analysis of T cell subpopulations revealed an increased frequency of CD4+ and CD8+ T cells in rheumatic heart disease. It is also suggested that CD8+ T cells with differential CD28 expression may be involved in the immune response in this condition. Importantly, our data demonstrated, for the first time, the expansion of double-negative (CD4-CD8-) T cells expressing the γδ T cell receptor (TCRγδ) in rheumatic heart disease and idiopathic cardiomyopathy, raising interest for further studies to elucidate the contribution of these cells in these diseases. Our study brings new insights into the immune response in different heart diseases. Also, the data indicates that Chagas cardiomyopathy is associated with a robust immunologic activation, possibly associated with the worse clinical outcome in relation to the other heart diseases evaluated.