Persistent Immunopathological Activity in Excised Valves from Rheumatic Heart Disease Patients in an Egyptian Cohort

Abstract

Rheumatic heart disease (RHD) is characterized by ongoing immune-mediated damage to the heart valves. T-lymphocyte infiltration was assessed in valvular tissue from 38 Egyptian patients (22 females, 16 males), selected for histological analysis from a total of 601 valve replacement and 344 valve repair procedures. The examined cases included individuals who underwent aortic valve replacement (n=22), and mitral valve replacement or repair (n=16). Immunohistochemical staining for CD4 and CD8 was conducted to assess the presence and distribution of T-cell subsets. Histological analysis was conducted using AxioScan ZEN Blue software, and quantitative measurements were performed using Fiji software. Our analysis revealed marked infiltration of both CD4⁺ and CD8⁺ T lymphocytes within affected valvular tissues, indicating ongoing immune activity. T-cells were distributed throughout all valve layers, with the highest expression localized in the fibrosa layer, as well as the heart valve endothelium. In addition, CD4⁺ and CD8⁺ positive staining was observed in small blood vessels within the valves, suggesting vascular participation in the inflammatory process. We further observed significantly greater CD4⁺ and CD8⁺ T-cell infiltration in mitral valves compared to aortic valves. Notably, CD4 and CD8 infiltration also showed a trend toward increased expression in females compared to male valve tissue. These findings highlight the persistent immunopathological nature of RHD and suggest distinct gender specific immune mechanisms in chronic valvular injury. Our results contribute to the growing understanding of the immunologic landscape in RHD and provide potential insights into targeted therapies.