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

• Published in: Pediatric allergy and immunology Vol. 36; no. 4; pp. e70092 - n/a
• Main Authors: Nemet, Shay, Elbirt, Daniel, Cohen, Ramon, Mahlab‐Guri, Keren, Bezalel‐Rosenberg, Shira, Asher, Ilan, Rubin, Limor, Talmon, Aviv, Ribak, Yaarit, Sergienko, Ruslan, Tal, Yuval, Shamriz, Oded
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.04.2025
• Subjects: Adolescent; Allergic rhinitis; Autoimmune diseases; Autoimmune Diseases - epidemiology; Autoimmunity; cancer; Child; Child, Preschool; Children; Female; Follow-Up Studies; Humans; IgE deficiency; immune dysregulation; Immunoglobulin E; Immunoglobulin E - blood; Immunoglobulin E - deficiency; Immunoglobulin M; inborn errors of immunity; Infant; Israel - epidemiology; Male; Malignancy; Neoplasms - epidemiology; Pediatrics; Population studies; Retrospective Studies; serum biomarkers; Solid tumors; Tumors; Israel; IgE deficiency; cancer; inborn errors of immunity; serum biomarkers; immune dysregulation
• ISSN: 0905-6157; 1399-3038; 1399-3038
• DOI: 10.1111/pai.70092

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.