IgE deficiency: the relationship with immunodeficiency, atopy and malignancy

Published: October 18, 2023

Immunoglobulin E (IgE), which is one of the five immunoglobulin classes, is essential for the allergic response. A normal IgE level is defined as a value less than 100 kU/L. Until recently, a very low or absent serum IgE level (IgE < 2.5 kU/L; also known as IgE deficiency) was considered normal. However, recent studies have shown that patients with IgE deficiency have significantly increased rates and risk for cancer. It is not yet known whether this is due to the role of IgE in recognizing and killing the cancerous cells, or if there may be an underlying immune abnormality as a singular cause. Some IgE deficient patients have normal levels of other immunoglobulins (normal IgG, IgA, IgM), whereas others may have different associated immune abnormalities, ranging from isolated low levels in a single immunoglobulin isotype or subclass, to having Common Variable Immunodeficiency (CVID). Additionally, some IgE deficient patients have positive skin testing to aeroallergens (defined as atopic individuals), while others have negative testing, also known as non-atopic individuals. The relationship between IgE deficiency, cancer and other immunologic and atopic characteristics is currently unknown.

In a retrospective study that was published in a recent issue of The Journal of Allergy and Clinical Immunology: In Practice, Agress et al. evaluated the association between a malignancy diagnosis and other immunological parameters (atopy and immunodeficiencies) in a large cohort of 408 IgE deficient adult patients. Demographics, comorbidities, and results of multiple tests were collected and analyzed.

Among those who had environmental skin testing performed for the evaluation of seasonal allergies, the non-atopic IgE deficient patients (those with negative environmental skin tests) were significantly more likely to have a malignancy diagnosis than those with positive skin tests (the atopic group). Additionally, IgE deficient individuals with malignancy were more likely to have an associated non-CVID humoral abnormality, low CD4 counts, IgM deficiency or IgG2 deficiency.

These results are the first to suggest that further laboratory evaluation and clinical follow up is necessary in patients with IgE deficiency. Close monitoring for cancer occurrence might be indicated specifically in non-atopic IgE deficient patients and in those with other associated abnormalities of the immune system. It is important to determine if patients with selective IgE deficiency and those with non-CVID humoral abnormality eventually progress towards a more severe immunodeficiency phenotype.

The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.

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