IGHE and immunoglobulin G4-related sclerosing disease: Importantly, clinical and epidemiologic evidence suggests that IgG4-RD and allergic entities are not manifestations of a single disease but rather distinct disease processes that both involve type 2 immune activation (18–20), overproduction of pro-Th2 cytokines, and the development of IgE- and IgG4-secreting B cells (21, 22).