Genetic defects in downregulation of IgE production and a new genetic classification of atopy

ABSTRACTAtopic disorders, such as asthma, eczema and rhinitis, develop due to the interactions between genetic and environmental factors. Atopy is characterized by enhanced IgE responses to environmental antigens. The production of IgE is upregulated by Th2 cytokines, in particular interleukin (IL)-4, and downregulated by Th1 cytokines, in particular interferon (IFN)-γ. In the present review, we present the genetic factors responsible for IgE production and genetic defects in the downregulation (brake) of IgE production, especially in terms of IL-12 and IL-18 signaling, mutations of the IL-12 receptor β2 chain gene and mutations of the IL-18 receptor α chain gene in atopy. Moreover, we newly present a genetic classification of atopy. There are four categories of genes that control the expression of allergic disorders, which include: (i) antigen recognition; (ii) IgE production (downregulation=brake; and upregulation); (iii) the production and release of mediators; and (iv) events on target organs. In the near future, this genetic classification will facilitate the development of tailor-made treatment