IgE deficiency (<2.5 IU/mL) in children: Clinical insights from a population-based study of 123,393 subjects

Background: Immunoglobulin (Ig)E deficiency (<2.5 IU/mL) in adults is linked to higher risks of cancer and autoimmunity, but its significance in children remains unclear. This study evaluates the clinical importance of IgE deficiency in a nationwide pediatric cohort. Methods: A retrospective, population-based study included 123,393 Israeli children tested for IgE levels between 2002 and 2022. Participants were categorized into four groups: deficient (<2.5 IU/mL), normal (2.5–100 IU/mL), high (100–1000 IU/mL), and very high (≥1000 IU/mL). Outcomes included cancer, inborn errors of immunity (IEI), and autoimmune disorders, with up to 5 years of follow-up. The data were analyzed using univariable methods and multivariable Cox regression. Results: Among the cohort, 2114 children (1.71%) had IgE deficiency, with a mean age of 3.73 years. Most (95.60%) were tested only once. IgE deficiency was associated with increased risks of solid tumors (HR = 2.721; 95% CI: 1.313–5.638), IEI (HR = 1.646; 95% CI: 1.095–2.474), and autoimmune disorders (HR = 1.266; 95% CI: 1.099–1.458) compared to normal IgE levels. No link was found between IgE deficiency and hematological malignancies. Selective IgM deficiency was the most common IEI associated with IgE deficiency (40%). Asthma prevalence was highest in children with very high IgE (N = 5574; 57.01%) and lowest in the normal IgE group (N = 24,171; 38.91%). The IgE-deficient group fell in the middle range (N = 903; 42.72%). In IgE-deficient children, allergic rhinitis was less common (11.26% vs. 14.09%). Conclusion: IgE deficiency in children is associated with higher risks of solid tumors, autoimmune disorders, and IEI, suggesting potential immune dysregulation. Close monitoring of IgE-deficient children should be considered.