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Inflammation Enhances the Risks of Stroke and Death in Chronic Chagas Disease Patients
Paulo Marcos Matta Guedes1, Cléber Mesquita de Andrade2, Daniela Ferreira Nunes3
1Department of Microbiology and Parasitology, Federal University of Rio Grande do Norte, Rio Grande do Norte, Natal, Brazil.
Insights
Inflammatory imbalance in Chagas disease patients is linked to increased death and stroke risk. Specific immune markers like IFN-γ and TNF-α were higher in high-risk patients, suggesting a role in disease progression.
Area of Science:
- Immunology
- Neurology
- Infectious Diseases
Background:
- Ischemic strokes are a significant cause of mortality in Chagas disease.
- Inflammation is a critical factor in ischemic stroke pathogenesis, including brain damage and repair.
- Understanding inflammatory markers in Chagas disease is crucial for assessing patient risk.
Purpose of the Study:
- To investigate the association between inflammatory markers and the risk of death and stroke in patients with chronic Chagas disease.
- To analyze the expression of various cytokines and transcription factors in different clinical forms of Chagas disease.
- To correlate inflammatory marker levels with death risk (DR) and stroke risk (SR).
Main Methods:
- Real-time PCR was used to analyze mRNA expression levels of cytokines, transcription factors (Th1, Th2, Th9, Th17, Th22, regulatory T cell), and iNOS in peripheral blood mononuclear cells.
- Patients with indeterminate, cardiac, digestive, and cardiodigestive forms of chronic Chagas disease were included.
- Transcript levels were correlated with DR and SR.
Main Results:
- Cardiac patients showed lower expression of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10, and IL-22, but higher IFN-γ and TNF-α compared to indeterminate patients.
- Cardiodigestive patients had higher TNF-α levels than indeterminate and digestive patients.
- High DR and SR were associated with lower GATA-3, FoxP3, and IL-10, and higher IFN-γ, TNF-α, and iNOS mRNA expression. Foxp3 and IL-10 negatively correlated with DR/SR, while TNF-α and iNOS positively correlated.
Conclusions:
- An inflammatory imbalance, characterized by specific cytokine and transcription factor profiles, is associated with increased death and stroke risk in chronic Chagas disease.
- The findings enhance understanding of stroke pathobiology in Chagas disease.
- This research may inform the development of therapeutic strategies to mitigate morbidity and mortality in Chagas disease patients.
Abstract:
Ischemic strokes have been implicated as a cause of death in Chagas disease patients. Inflammation has been recognized as a key component in all ischemic processes, including the intravascular events triggered by vessel interruption, brain damage and repair. In this study, we evaluated the association between inflammatory markers and the death risk (DR) and stroke risk (SR) of patients with different clinical forms of chronic Chagas disease. The mRNA expression levels of cytokines, transcription factors expressed in the adaptive immune response (Th1, Th2, Th9, Th17, Th22 and regulatory T cell), and iNOS were analyzed by real-time PCR in peripheral blood mononuclear cells of chagasic patients who exhibited the indeterminate, cardiac, digestive and cardiodigestive clinical forms of the disease, and the levels of these transcripts were correlated with the DR and SR. Cardiac patients exhibited lower mRNA expression levels of GATA-3, FoxP3, AHR, IL-4, IL-9, IL-10 and IL-22 but exhibited higher expression of IFN-γ and TNF-α compared with indeterminate patients. Digestive patients showed similar levels of GATA-3, IL-4 and IL-10 than indeterminate patients. Cardiodigestive patients exhibited higher levels of TNF-α compared with indeterminate and digestive patients. Furthermore, we demonstrated that patients with high DR and SR exhibited lower GATA-3, FoxP3, and IL-10 expression and higher IFN-γ, TNF-α and iNOS mRNA expression than patients with low DR and SR. A negative correlation was observed between Foxp3 and IL-10 mRNA expression and the DR and SR. Moreover, TNF-α and iNOS expression was positively correlated with DR and SR. Our data suggest that an inflammatory imbalance in chronic Chagas disease patients is associated with a high DR and SR. This study provides a better understanding of the stroke pathobiology in the general population and might aid the development of therapeutic strategies for controlling the morbidity and mortality of Chagas disease.
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