Certain allele combinations appear to increase RHD autoimmune susceptibility. Human leukocyte antigen (HLA) class II allele DR7 (HLA-DR7) is most often associated with RHD, and its combination with certain DQ alleles is seemingly associated with the development of valvular lesions. The mechanism by which MHC class II molecules increase a hosts susceptibility to autoimmune reactions in RHD is unknown, but it is likely related to the role HLA molecules play in presenting antigens to T cell receptors, thus triggering an immune response. Also found on human chromosome 6 is the cytokine TNF-α which is also associated with RHD. High expression levels of TNF-α may exacerbate valvular tissue inflammation, contributing to RHD pathogenesis. Mannose-binding lectin (MBL) is an inflammatory protein involved in pathogen recognition. Different variants of MBL2 gene regions are associated in RHD. RHD-induced mitral valve stenosis has been associated with MBL2 alleles encoding for high production of MBL. Aortic valve regurgitation in RHD patients has been associated with different MBL2 alleles that encode for low production of MBL. Other genes are also being investigated to better understand the complexity of autoimmune reactions that occur in RHD. Diagnosis
Modified Jones criteria were first published in 1944 by T. Duckett Jones, MD. They have been periodically revised by the American Heart Association in collaboration with other groups.
Characteristic Aschoff bodies, composed of swollen eosinophilic collagen surrounded by lymphocytes and macrophages can be seen on light microscopy. The larger macrophages may become Anitschkow cells or Aschoff giant cells. Rheumatic valvular lesions may also involve a cell-mediated immunity reaction as these lesions predominantly contain T-helper cells and macrophages.In rheumatic fever, these lesions can be found in any layer of the heart causing different types of carditis. The inflammation may cause a serofibrinous pericardial exudate described as "bread-and-butter" pericarditis, which usually resolves without sequelae. Involvement of the endocardium typically results in fibrinoid necrosis and wart formation along the lines of closure of the left-sided heart valves. Warty projections arise from the deposition, while subendocardial lesions may induce irregular thickenings called MacCallum plaques. Rheumatic heart disease
Chronic rheumatic heart disease (RHD) is characterized by repeated inflammation with fibrinous repair. The cardinal anatomic changes of the valve include leaflet thickening, commissural fusion, and shortening and thickening of the tendinous cords. It is caused by an autoimmune reaction to Group A β-hemolytic streptococci (GAS) that results in valvular damage. Fibrosis and scarring of valve leaflets, commissures and cusps leads to abnormalities that can result in valve stenosis or regurgitation. The inflammation caused by rheumatic fever, usually during childhood, is referred to as rheumatic valvulitis. About half of patients with rheumatic fever develop inflammation involving valvular endothelium. The majority of morbidity and mortality associated with rheumatic fever is caused by its destructive effects on cardiac valve tissue.