Increased malignancy incidence in IgE deficient patients not due to concomitant Common Variable Immunodeficiency

Background: Immunoglobulin E (IgE) deficiency (<2.5 kU/L) has unclear clinical significance. Very little is known about the clinical characteristics of IgE deficiency in patients with Common Variable Immunodeficiency (CVID). Objective: To evaluate the clinical and laboratory differences between patients with IgE deficiency and those with non-IgE deficiency with and without CVID diagnosis. Methods: This is a retrospective study of adult patients who had total serum IgE levels measured at our facility from 2010 through 2015. Patients with IgE levels lower than 2.5 kU/L composed the IgE deficiency group. We used Clinical Looking Glass software to identify laboratory results and comorbid conditions including CVID and malignancy. Results: The IgE levels were measured in 2,339 patients and 63 (2.7%) had IgE deficiency. Of those with IgE deficiency, 14 of 63 (22%) had CVID diagnosis compared with only 62 of 2,276 patients (2.7%) with non-IgE deficiency and CVID. A significantly higher rate of prior malignancy was found in patients with IgE deficiency (21 of 63, 33%) compared with those with non-IgE deficiency (197 of 2,276, 8.7%; P = .001; odds ratio 5.51, 95% confidence interval 3.07-9.88). Six of 14 patients with CVID and IgE deficiency (43%) had a prior malignancy diagnosis compared with 8 of 62 patients (13%) with CVID and non-IgE deficiency (P = .009; odds ratio 10.65, 95% confidence interval 1.79-63.19). In addition to the higher rate of malignancy, patients with CVID and IgE deficiency did not have more severe disease than those with CVID and non-IgE deficiency. Conclusion: The rate of prior malignancy is significantly higher in patients with IgE deficiency than in those without IgE deficiency. Similarly, patients with CVID and IgE deficiency have a higher frequency of prior malignancy than those with CVID and non-IgE deficiency. However, patients with IgE deficiency have higher frequency of malignancy than patients with normal IgE levels even in the absence of CVID.