Identification of Interleukin-1β in Whole Blood as a Candidate Biomarker for Alcohol Use Disorder Risk Based on AUDIT Scores

IF 2.6 3区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Irina Balan, Alejandro G. Lopez, Thomas Gilmore, Michael Bremmer, Todd K. O'Buckley, Kai Xia, Christian S. Hendershot, A. Leslie Morrow
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Abstract

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.

Abstract Image

基于审计评分的全血白细胞介素-1β作为酒精使用障碍风险的候选生物标志物的鉴定
酒精使用障碍(AUD)与慢性炎症和免疫失调有关,但没有有效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,确定全血中白细胞介素-1β (IL-1β)是AUD风险的一个有希望的候选生物标志物。28名未寻求治疗的成年人提供了全血样本,审计得分在2到22之间。我们的目的是确定与早期审计评分风险相关的免疫变化信号的生物标志物,干预可能是最有效的。Luminex多重免疫测定法在联合细胞裂解液和上清液中定量了14种免疫相关介质。IL-1β、IL-18、IL-7和CCL11在审计评分较高的个体中显著升高。IL-1β显示出最大的效应量(Cohen's d),并且是随机森林和线性回归分析中审计和审计消耗(审计- c)得分的最一致的预测因子。适度多元回归(MMR)证实,IL-1β预测两项评分独立于其他免疫介质。受试者工作特征(ROC)分析显示了鉴别潜力,对于AUDIT≥6(真阳性率[TPR] = 0.71,假阳性率[FPR] = 0.14), IL-1β的AUC为0.81(良好鉴别),对于AUDIT- c阈值(TPR = 0.80, FPR = 0.00), AUC为0.94(良好鉴别)。主成分分析(PCA)显示高危人群的免疫变异性更大,特别是在促炎介质中,提示免疫失调。这项研究展示了将全血免疫分析与高灵敏度多重免疫分析相结合的实用性,并应用传统的统计方法和机器学习来探索AUD风险的潜在生物标志物。IL-1β是通过AUDIT评分评估AUD风险的统计学上可靠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复制,以确定它们在成瘾医学中的转化潜力。
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来源期刊
Addiction Biology
Addiction Biology 生物-生化与分子生物学
CiteScore
8.10
自引率
2.90%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields. Addiction Biology includes peer-reviewed original research reports and reviews. Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.
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