IGHE and type 1 diabetes mellitus: Most importantly, only Subtype 2, the second major group, without anti-GAD antibody or elevation of IgE as described above, was associated with TYK2 promoter variant, suggestive of deteriorated IFN response to resist against virus infections (Nagafuchi et al., 2015), and may be related to virus-induced diabetes, thereby enhancing the validity of subtyping of T1D as presented by this study.