IGHE and allergic disease: IL-4 is known to provide positive feedback to Th 2 cells and induce B isoform cells to differentiate into IgE antibody-producing cells, which is a major mediator and activator of allergic reactions, by inducing mitogen-activated protein kinase (MAPK) activation through the nuclear factor kappa-light-chain-enhancer of the activated B cells (NFκB) pathway to increase intracellular calcium and simultaneously induce histamine secretion [30,31].