IGHG3 and rheumatic heart disease: While we propose mechanisms in a hypothesis where GlcNAc-specific IgG2 could play a dominant role in RHD to direct the T cell subsets to the valve, IgG3 cannot be discounted and must be considered for its potential role in RHD where IgG3 would strongly direct complement-mediated cytotoxicity, an effector function largely absent from IgG2 (75).