AllergoOncology: ultra-low IgE, a potential novel biomarker in cancer—a Position Paper of the European Academy of Allergy and Clinical Immunology (EAACI)

Abstract

Elevated serum IgE levels are associated with allergic disorders, parasitosis and specific immunologic abnormalities. In addition, epidemiological and mechanistic evidence indicates an association between IgE-mediated immune surveillance and protection from tumour growth. Intriguingly, recent studies reveal a correlation between IgE deficiency and increased malignancy risk. This is the first review discussing IgE levels and links to pathological conditions, with special focus on the potential clinical significance of ultra-low serum IgE levels and risk of malignancy. In this Position Paper we discuss: (a) the utility of measuring total IgE levels in the management of allergies, parasitosis, and immunodeficiencies, (b) factors that may influence serum IgE levels, (c) IgE as a marker of different disorders, and d) the relationship between ultra-low IgE levels and malignancy susceptibility. While elevated serum IgE is generally associated with allergic/atopic conditions, very low or absent IgE may hamper anti-tumour surveillance, indicating the importance of a balanced IgE-mediated immune function. Ultra-low IgE may prove to be an unexpected biomarker for cancer risk. Nevertheless, given the early stage of investigations conducted mostly in patients with diseases that influence IgE levels, in-depth mechanistic studies and stratification of malignancy risk based on associated demographic, immunological and clinical co-factors are warranted.

IgE Activates Monocytes from Cancer Patients to Acquire a Pro-Inflammatory Phenotype

“…Furthermore, it has been shown that there were no significant differences between the number of FcεRI receptors on monocytes in healthy volunteers and allergic patients [15]. Interestingly, recent reports suggest that patients with IgE deficiency have higher risk of developing malignancies [48,49]. It is possible that IgE deficient patients with cancer, whose IgE receptors may be mostly unoccupied, may also benefit from treatment with tumour antigen-specific IgE immunotherapy to prompt immune cell activation and cytotoxic killing of target tumour cells.…”

Anti-IgE for the Treatment of Chronic Urticaria

“…Very low or absent IgE was shown to impede anti-tumour surveillance and there is evidence that ultra-low IgE might serve as a biomarker for cancer risk. 62 Nevertheless, hitherto existing data from omalizumab in clinical studies and post-marketing do not indicate striking incidence rates for malignancies, such as non-melanoma skin cancer. 63 Indeed, a recent systematic review and meta-analysis reported that patients receiving long-term omalizumab were not significantly more likely to develop study-emergent solid epithelial cancer than those receiving standard treatment.…”

Will Research on COVID-19 Stimulate the Identification of Immunological Mechanisms Underlying Some Protective Effects?

“…In particular, ultra-low IgE is likely to be an unexpected biomarker for cancer risk. Even in this study, the authors suggest the need for in-depth mechanistic studies and cancer risk stratification based on demographic and immunological characteristics and possible clinical cofactors ( 5 ).…”