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.