Low serum IgE is associated with an increased risk of chronic lymphocytic leukemia: a large retrospective cohort study

Introduction Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia in the western world. Its pathophysiology is intertwined with immune dysfunction. Emerging evidence suggests an inverse association between serum immunoglobulin E (IgE) and hematologic malignancies, but previous studies linking low IgE to CLL risk were limited by small cohorts and a lack of adjustment for confounding factors, particularly hypogammaglobulinemia. Purpose This study aimed to evaluate the association between low serum IgE levels and the future development of CLL in a large, real-world cohort, while accounting for other immunoglobulins and confounding factors. Methods We conducted a retrospective quantitative observational study of 118,740 adults from a large health maintenance organization. The primary exposure was a baseline IgE level of less than 25 IU/mL. We used Kaplan-Meier curves and a multivariable Cox proportional hazards model to assess the association between low IgE and CLL diagnosis over a seven-year follow-up period, adjusting for age, sex, and other potential confounders, including hypogammaglobulinemia and atopy-related conditions. Results A serum IgE level of less than 25 IU/mL was significantly associated with an increased hazard of developing CLL (HR = 1.94, 97.5% CI: 1.47–2.56). This association persisted after adjusting for all confounding variables. Established risk factors, such as older age (HR = 1.07) and male sex (HR = 1.82), were also significant. Kaplan-Meier curves showed a sustained and a statistically significant increased risk in the low IgE group throughout the follow-up period. Conclusion Lower serum IgE levels are independently associated with an increased risk of developing CLL.