Redox-immunological imbalance is associated with clinical stages of Chagas cardiomyopathy: A cross-sectional study

Abstract

Background: Chronic Chagas disease progresses through distinct clinical stages, from an asymptomatic form to severe cardiomyopathy. This multicenter, cross-sectional study aimed to characterize the systemic and cellular immune and oxidative profiles associated with each clinical stage. Methods: Seropositive individuals for Chagas disease were recruited through a multicentric approach across three public hospitals in Argentina and classified as having no demonstrable pathology (NDP), mild to moderate cardiomyopathy (MCC), or severe cardiomyopathy (SCC). Healthy individuals (HI), seronegative for Chagas disease were included as the control group. Plasma immune and redox status was assessed through cytokine levels, antioxidant enzyme activity, and markers of tissue damage. Using peripheral blood mononuclear cells, we evaluated oxidative stress and the expression of genes involved in pro-inflammatory, anti-inflammatory, and Nrf2-regulated antioxidant responses. Receiver Operating Characteristic (ROC) analyses were conducted to evaluate the ability of plasma Superoxide dismutase (SOD) activity to discriminate between clinical stages as a potential biomarker. Results: NDP individuals displayed a pattern of selective immune activation along with increased antioxidant responses and elevated plasmatic SOD activity, suggesting a balanced systemic immuno-oxidative state. In contrast, MCC and SCC stages exhibited broader inflammatory response, higher ROS levels, and reduced antioxidant defenses. Plasma SOD activity declined with disease severity and showed strong discriminatory capacity between stages. Conclusions: These findings highlight state-associated immunoredox imbalance as a key feature of Chagas' cardiomyopathy. While further studies are needed, superoxide dismutase activity is emerging as a promising minimally invasive biomarker for monitoring the stages of this infectious disease.