Abstract
BACKGROUND: Vitamin D has immunomodulatory functions that may influence allergic disease, while total immunoglobulin E (IgE) is a biomarker of allergic sensitization. Prior studies of serum 25-hydroxyvitamin D [25(OH)D] and IgE have been inconsistent. This study aimed to clarify their relationship in a large pediatric cohort. METHODS: We analyzed 9,126 children (age 1-18 years; median 6.0 years) at a tertiary pediatric center. Serum 25(OH)D and total IgE were measured by electrochemiluminescence immunoassay. Vitamin D status was defined as deficient (<30 ng/mL), insufficient (30-50 ng/mL), or sufficient (>50 ng/mL). Analyses included Spearman correlation, multivariable regression, restricted cubic spline (RCS), and stratification by age, sex, and season. RESULTS: Serum 25(OH)D and IgE were inversely correlated (r=-0.1443, P<0.0001), and this association was stronger in allergic (r=-0.2662) than non-allergic (r=-0.1354) children. Regression confirmed 25(OH)D as an independent negative predictor of IgE (β=-0.0081, P<0.0001). RCS analysis revealed a non-linear association between serum 25(OH)D and total IgE concentrations, with higher IgE levels predominantly observed at lower 25(OH)D concentrations and a less pronounced association at higher levels. Stratification revealed the strongest effect in children ≤6 years, comparable results by sex, and a stronger winter association. IgE was highest in vitamin D-deficient and lowest in sufficient groups (P<0.0001). CONCLUSIONS: Serum 25(OH)D is inversely associated with IgE, with age- and season-dependent variation in this association. These findings highlight an association between vitamin D status and allergic sensitization at the population level and support further investigation, while not establishing causality or therapeutic benefit.