This deficiency elicits a cascade of cellular and humoral changes which impact the immune system, namely: the production of defective NK T-cells, CD8 T-cells, and the impaired function and generation of Th17-cells, NK cells, and antiviral cytokines [13,14]. These consequences in conjunction with the cytokine secretion abnormalities and severe decrease in the production of IL-2, TNF-α, and IFN-γ commonly seen in AR-HIES patients [15,16], result in a strong skewing towards the production of Th2 CD4+ T-cell [17]. This evidence concerns the gene TNF and hyper-IgE syndrome.