The Pathogenesis of Rheumatic Heart Disease with Unsettled Issues

In underdeveloped nations like India, rheumatic heart disease (RHD) is a serious public health concern that significantly increases cardiac morbidity and mortality. It is a progressive form of heart valves damage that leads to dysfunction of the heart. According to WHO 2020, It is urgently necessary to clarify the pathogenic mechanisms underlying RHD in order to develop therapeutic interventions. Molecular mimicry (MM), the fundamental mechanism underlying RHD, is triggered by antigens on group A streptococcus (GAS) to activate CD4 + T cells, which subsequently cross-react with related peptides in the tissue surrounding the heart valve. Although, the most well-established theory for the development of RHD is MM, however, over the past few years, competence of MM theory to elucidate autoimmune diseases in RHD is questioned several times. The GAS first adheres and colonize on the surface of epithelium of the heart and then with the help of various adhesion molecules invade the heart valves and cause inflammation. Furthermore, the observation that multiple members of the affected person's family have RHD supports the idea that genetics plays a role in the RHD pathogenesis. This suggests a genetic predisposition for RHD. Therefore, in the present review, besides MM, other factors such as cellular proteins, various cells producing cytokines and chemokines, and genetic factors that leads to disease manifestation have been discussed.