The IgG2 deposition on valve and heart tissues and elevated anti-GlcNAc antibodies in RHD sera combined with a lower GlcNAc-specific IgG2 response in pharyngitis suggests disease specificity and ultimately IgG2 may be responsible for directing infiltration of Th1 and Th17A cell subsets as well as potential cytotoxic IgG3 responses to the valve. Here, IGHG3 is linked to rheumatic heart disease.