Neutrophil Elastase (ELANE) as a Novel Neuroinflammatory Biomarker in Alcohol Use Disorder: Clinical Validation

Alcohol use disorder is a severe public health problem; however, the specific mechanisms remain unclear. Our previous studies have identified 'ELANE' as the Hub gene in alcohol use disorder. However, its role in the clinical practice of alcohol use disorders has not been confirmed. A total of 53 healthy controls and 90 patients with alcohol use disorders were enrolled. Clinical factors were gathered, and a 1-year relapse follow-up was carried out. The group with alcohol use disorder had considerably higher ELANE concentrations than the healthy controls (p < 0.001). Patients were categorized as high ELANE (≥ 2.7651 pg/mL, n = 46) or low ELANE (< 2.7651 pg/mL, n = 44) based on the median ELANE expression level in the alcohol use disorder group. SERPINA3 was statistically significant, according to binary logistic analysis (p = 0.007). After 12 months of follow-up, there was no difference in event-free survival between patients with low and high ELANE levels, according to Kaplan-Meier survival analysis (p = 0.568). ELANE had an area under the curve of 0.8683 (p < 0.0001), according to receiver characteristic curve analysis, and a sensitivity and specificity of 65.6% and 92.5%, respectively. According to Cox regression analysis, marital status was a negative predictor of relapse (β = -0.661; hazard ratio = 0.516; p = 0.038). Plasma ELANE represents a promising neuroinflammatory biomarker for AUD diagnosis, demonstrating excellent specificity albeit moderate sensitivity. The protease-antiprotease imbalance reflected by elevated ELANE and relatively decreased SERPINA3 suggests dysregulated inflammatory homeostasis in AUD. While ELANE lacks prognostic utility for relapse prediction, these findings warrant further investigation of neutrophil elastase inhibitors as potential therapeutic interventions and highlight the critical importance of social support systems in AUD recovery.