Elevated as well as persistent IgG2 concentrations from repeated streptococcal infections may begin the inflammatory cascade at the valve endothelial surface for further injury by inflammatory T cell subsets Th1 and Th17 and the potential for enhanced fibrosis in the presence of the TGF-β1 gene variants found in RHD (49). The gene discussed is TGFB1; the disease is streptococcal infection.