The Association Between Malignancy, Immunodeficiency, and Atopy in IgE-Deficient Patients

Background: Studies show that IgE-deficient patients (IgE <2.5 kU/L) have a high prevalence of malignancy, but relevant clinical and laboratory characteristics associated with this susceptibility have never been well characterized. Objective: To evaluate if there is an association between a malignancy diagnosis and other immunological parameters (atopy or other immune abnormalities) in IgE-deficient patients. Methods: We retrospectively analyzed medical records of 408 IgE-deficient adults seen at our institution between 2005 and 2020. Results: A malignancy diagnosis was found in 23.5% (96 of 408) of IgE-deficient patients. Among those who had allergy skin testing performed for allergic rhinitis–like symptoms, the nonatopic IgE-deficient patients (negative environmental skin tests) were more likely to have a malignancy diagnosis than the atopic group (odds ratio [OR] = 4.36, 95% confidence interval [CI]: 1.11-17.13, P =.03). The IgE-deficient individuals with an additional non–common variable immunodeficiency (non-CVID) humoral abnormality (n = 75; with low IgG, IgA, or IgM without meeting criteria for CVID) were more likely to have a malignancy diagnosis than those with only a selective IgE deficiency (n = 134; with normal IgA, IgM, and IgG) (OR = 2.79, 95% CI: 1.37-5.68, P =.005). Among the IgE-deficient patients, certain less well-defined immune abnormalities such as IgM deficiency (OR = 2.46, 95% CI: 1.13-5.36, P =.02), IgG2 deficiency (OR = 10.14, 95% CI: 1.9-54.1, P =.007), and CD4 lymphopenia (OR = 7.81, 95% CI: 2.21-27.63, P =.001) were associated with higher malignancy odds than those without these abnormalities. Conclusion: The odds of a malignancy diagnosis are not shared equally by all IgE-deficient patients. Prospective studies are needed to determine the utility of performing skin testing and measuring additional immunological parameters in assessing the long-term malignancy risk in IgE-deficient patients.