Dados do Trabalho

Título

Evaluation of Systemic Immunological Factors in Rheumatic Heart Disease: Association with Restenosis and Disease Severity.

Introdução

Rheumatic Heart Disease (RHD), a condition prevalent in low-income and developing countries, is characterized by valvular insufficiency resulting from infection by Streptococcus pyogenes. The pathogenesis of RHD involves antigenic mimicry between bacterial and valvular proteins, which triggers a persistent immune response mediated by inflammatory and fibrotic molecules, leading to valvular tissue remodeling and damage. In Brazil, most valve interventions, especially for the mitral valve, are due to RHD. Percutaneous Mitral Valvuloplasty (PMV) is a minimally invasive procedure for the treatment of severe valvular stenosis.

Objetivo (s)

In this study, we assessed the expression of systemic immunological factors in patients with RHD who underwent and did not undergo PMV, with the aim of identifying biomarkers of disease severity and progression.

Material e Métodos

Plasma levels of immunological molecules were measured using the Bio-Plex Pro Human Cytokine Standard 27-plex kit (Biorad), and their associations with other signaling pathways were determined using the KEGG database. Patient groups comprised those with severe RHD who underwent PMV (n=53) and those who, despite being affected, did not undergo PMV (n=28). A 5 year follow-up analysis was conducted on 7 patients who underwent PMV and either developed or did not develop restenosis (COEP ETIC528/08).

Resultados e Conclusão

Results: We found elevated plasma levels of cytokines (IL-1β, IL-1Ra, IFN-γ, IL-17, IL-2, IL-4, IL-6), chemokines (CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL10, CCL11), and fibrotic factors (basic FGF, PDGF, G-CSF) in patients with RHD who underwent PMV compared to those who did not. Pathway enrichment analysis indicated the involvement of these elevated molecules in cytokine-cytokine receptor and IL-17 signaling pathways, along with significant immune activation associated with PMV. Furthermore, the occurrence of restenosis during a 5-year follow-up was associated with increased levels of IFN-γ, IL-9, and IL-1β compared to baseline levels. Conclusion: Intense systemic immune activation was observed in patients with RHD who underwent PMV, along with persistent inflammation among these patients 5 years after the surgical procedure, suggesting that inflammatory cytokines, chemokines, and fibrotic factors are predictors of severity in RHD.

Palavras Chave

Rheumatic Heart Disease; Immunology; Immune Response in Cardiovascular Disease