Balan Irina, Lopez Alejandro G, Gilmore Thomas, Bremmer Michael, O'Buckley Todd K, Xia Kai, Hendershot Christian S, Morrow A Leslie
Bowles Center for Alcohol Studies, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Psychiatry, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Addict Biol. 2025 Sep;30(9):e70088. doi: 10.1111/adb.70088.
Alcohol use disorder (AUD) is associated with chronic inflammation and immune dysregulation, yet no validated immune-based markers exist to support assessment or monitoring. This study identifies interleukin-1 beta (IL-1β) in whole blood as a promising candidate biomarker of AUD risk, based on Alcohol Use Disorders Identification Test (AUDIT) scores. Twenty-eight non-treatment-seeking adults, with AUDIT scores between 2 and 22, provided whole blood samples. We aimed to identify biomarkers that signal immune changes associated with early AUDIT score risk, where interventions may be most effective. Luminex multiplex immunoassays quantified 14 immune-related mediators in combined cell lysates and supernatants. IL-1β, IL-18, IL-7 and CCL11 were significantly elevated in individuals with higher AUDIT scores. IL-1β showed the largest effect size (Cohen's d) and was the most consistent predictor of both AUDIT and AUDIT-Consumption (AUDIT-C) scores across random forest and linear regression analyses. Moderated multiple regression (MMR) confirmed that IL-1β predicted both scores independent of other immune mediators. Receiver operating characteristic (ROC) analyses demonstrated discriminative potential, with IL-1β achieving an AUC of 0.81 (good discrimination) for AUDIT ≥ 6 (true positive rate [TPR] = 0.71; false positive rate [FPR] = 0.14) and an AUC of 0.94 (excellent discrimination) for AUDIT-C thresholds (TPR = 0.80; FPR = 0.00). Principal component analysis (PCA) revealed greater immune variability in the high-risk group, particularly among proinflammatory mediators, suggesting immune dysregulation. This study demonstrates the utility of integrating whole blood immune profiling with high-sensitivity multiplex immunoassays, and applying both traditional statistical methods and machine learning to explore potential biomarkers for AUD risk. IL-1β is a statistically robust and clinically relevant candidate biomarker of AUD risk assessed by AUDIT scores. These findings require replication in larger, independent samples to determine their translational potential in addiction medicine.
酒精使用障碍（AUD）与慢性炎症和免疫失调相关，但目前尚无经过验证的基于免疫的标志物来支持评估或监测。本研究基于酒精使用障碍识别测试（AUDIT）分数，确定全血中的白细胞介素-1β（IL-1β）是AUD风险的一个有前景的候选生物标志物。28名未寻求治疗的成年人，AUDIT分数在2至22之间，提供了全血样本。我们旨在识别与早期AUDIT分数风险相关的免疫变化的生物标志物，此时干预可能最为有效。Luminex多重免疫分析法定量了细胞裂解物和上清液中14种免疫相关介质。AUDIT分数较高的个体中，IL-1β、IL-18、IL-7和CCL11显著升高。IL-1β显示出最大的效应量（科恩d值），并且在随机森林和线性回归分析中是AUDIT和酒精使用障碍识别测试-饮酒量（AUDIT-C）分数最一致的预测因子。调节多元回归（MMR）证实，IL-1β独立于其他免疫介质预测这两个分数。受试者工作特征（ROC）分析显示出判别潜力，对于AUDIT≥6，IL-1β的曲线下面积（AUC）为0.81（良好判别）（真阳性率[TPR]=0.71；假阳性率[FPR]=0.14），对于AUDIT-C阈值，AUC为0.94（优秀判别）（TPR=0.80；FPR=0.00）。主成分分析（PCA）显示高危组的免疫变异性更大，尤其是在促炎介质中，表明存在免疫失调。本研究证明了将全血免疫谱分析与高灵敏度多重免疫分析相结合，并应用传统统计方法和机器学习来探索AUD风险潜在生物标志物的实用性。IL-1β是通过AUDIT分数评估的AUD风险的一个统计学上稳健且临床相关的候选生物标志物。这些发现需要在更大的独立样本中进行重复验证，以确定它们在成瘾医学中的转化潜力。
