The other side of the coin: IgE deficiency, a susceptibility factor for malignancy occurrence

Since the discovery of IgE, almost all attention was given to conditions with elevated specific or total IgE levels such as atopy, type I hypersensitivity reactions, or parasitic infestations. Recent prospective and retrospective studies show that having very low IgE levels, such as those seen in IgE deficiency (IgE<2.5 kU/L), is not without clinical consequences. Patients with ultra-low IgE levels have an elevated risk of cancer of any type. These results are in agreement with murine models research which demonstrated that grafted tumors grow faster and bigger on an IgE knockout background. The novel finding that IgE deficiency is a susceptibility factor for cancer, fits very well with the AllergoOncology concept. The reports on a beneficial, cytotoxic function of IgE, in cooperation with its high (FcεRI) and low (FcεRII, CD23) affinity IgE receptors resulting in tumor cell phagocytosis, propose a role of IgE in cancer surveillance. It appears that not only deficiency of serum IgE, but also lack of tissue-bound IgE is important in malignancy susceptibility in these patients. As such, IgE deficient individuals with absent serum and cell-bound IgE as suggested by negative type I hypersensitivity skin tests, are at the highest risk for a malignancy diagnosis. In contrast, IgE deficient individuals with cell-bound IgE depicted through positive type I hypersensitivity skin tests, have lower rates of malignancy diagnosis. The present report discusses the evidence and potential role of ultra-low IgE as a novel biomarker for cancer susceptibility.