IGHE and Alzheimer disease: Conversely, these events cause Treg deficiency, one of the hallmarks of AD pathogenesis.34,92–95 Furthermore, CpG hypermethylation in IL-4 is negatively correlated with serum total IgE levels, explaining the role of Th2 immunity in AD.96 Enhanced hypermethylation of S100 calcium binding protein A5 (S100A5) was found in the epidermal part of lesions in AD cases in comparison with healthy individuals.97 Hypomethylation was observed in Recombinant Keratin 6 A (KRT6A) in keratinocytes, and methylation of cg07548383 in FLG also elevates AD risk.98