Immunometabolic Alterations in Alopecia Areata: Exploratory Evaluation of Serum Leptin, Vitamin D, and Metabolic Parameters

Background: Alopecia areata (AA) is a T-cell-mediated autoimmune disease. Leptin, a proinflammatory adipokine, is thought to modulate immune responses and contribute to immunometabolic regulation in inflammatory diseases. Objectives: This study aimed to evaluate serum leptin levels in AA patients and investigate their relationship with clinical characteristics, metabolic syndrome (MS) components, and nutritional markers like Vitamin B12 and D. Methods: A cross-sectional, STROBE-compliant study was conducted with 35 AA patients and 31 healthy controls. Serum leptin, Vitamin B12, 25(OH)D, fasting glucose, and lipid profiles were measured. Analyses included group comparisons, correlations, and ANCOVA and regression models adjusted for age, sex, and BMI. Results: Serum leptin levels did not differ between groups (p=0.480). In patients, leptin correlated negatively with disease onset age (r=−0.449, p=0.007); this association persisted after adjustment for sex and BMI (p=0.002) but not after further adjustment for current age (p=0.559), with which onset age was highly collinear. Serum 25(OH)D was lower in patients (p<0.001; significant after Bonferroni correction) and remained nominally lower after adjustment for age, sex, and BMI (p=0.006). Differences in vitamin B12 and fasting glucose did not survive Bonferroni correction and were considered exploratory. MS prevalence was 11.4% in patients and 0% in controls (p=0.116). Conclusions: Serum leptin did not differ between groups, and its association with disease onset age could not be separated from an effect of current age; a biological role for leptin in AA is not excluded. Lower serum 25(OH)D was the most consistent finding. All associations should be considered hypothesis-generating.