Hyper-IgE syndrome (HIES) associated with loss-of-function (LOF) mutations in the STAT3 gene (STAT3 LOF HIES) (1, 2) with resultant deficiency of TH17 cells and its secreted cytokine IL-17 (3–5), are now known to underlie majority of the sporadic and autosomal dominant forms of HIES. This evidence concerns the gene STAT3 and hyper-IgE syndrome.