Inflammation in mitral stenosis due to rheumatic heart disease: a genetic and histological study

Introduction. Rheumatic heart disease is an acquired heart condition resulting from an autoimmune reaction to gram-positive Streptococcus pyogenes in a genetically predisposed host. Although in recent years degenerative valve diseases (such as aortic valve calcification) have become more common among acquired heart defects, rheumatic heart disease remains a significant heart issue diagnosed in about 33 million people worldwide. We aimed to analyze local expression of cytokines and immune cell markers in the native mitral heart valves affected by stenosis caused by rheumatic heart disease. Materials and methods. We studied native mitral valves affected by stenosis caused by rheumatic heart disease (n=19) and native aortic valves affected by calcific aortic stenosis (n=21). Immunohistochemical staining to the following markers was performed: CD45, CD68, CD3, CD19, myeloperoxidase (MPO), and CD31. Gene expression was analyzed with real-time quantitative polymerase chain reaction. Results. In native valve leaflets, we detected inflammatory infiltrates represented by CD68+, CD45+, CD3+, and CD31+ cells. Moreover, the studied valves were characterized by intense neovascularization. Furthermore, a high infiltration of MPO+ and CD19+ cells was observed in the mitral valves. Gene expression analysis demonstrated the upregulation of IL1B, IL6, IL8, and TNFα and the downregulation of IL33, CCL4,andCXCL1 in the native valves of patients with mitral stenosis caused by rheumatic heart disease. Conclusion. The native mitral valves affected by stenosis are characterized by a local inflammatory response, foci of neovascularization, and aggressive infiltration of neutrophils and B-lymphocytes compared to the aortic native valves affected by calcific aortic stenosis. Keywords: rheumatic heart disease, mitral stenosis, aortic stenosis, gene expression, immune cells, inflammation