补体系统
补体因子I
酒精性肝炎
蛋白质组
补体成分5
免疫学
医学
肝硬化
炎症
CD46型
转甲状腺素
血液蛋白质类
系数H
内科学
酒精性肝病
生物
抗体
生物信息学
作者
Moyinoluwa Taiwo,Emily Huang,Vai Pathak,Annette Bellar,Nicole Welch,Jaividhya Dasarathy,David Streem,Craig J. McClain,Mack C. Mitchell,Bruce Barton,Gyöngyi Szabó,Srinivasan Dasarathy,Esperance Schaefer,Jay Luther,Le Day,Xinshou Ouyang,Suyavaran Arumugam,Wajahat Z. Mehal,Jon Jacobs,Rachel Goodman,Daniel M. Rotroff,Laura E. Nagy
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2024-04-04
标识
DOI:10.1172/jci.insight.174127
摘要
Diagnostic challenges continue to impede development of effective therapies for successful management of alcohol-associated hepatitis (AH), thus creating an unmet need to identify and develop non-invasive biomarkers for AH. In murine models of ethanol-induced liver injury, complement activation contributes to hepatic inflammation and injury. Therefore, we hypothesized that complement proteins could be rational diagnostic/prognostic biomarkers in AH. Here, we performed a comparative analysis of data derived from the human hepatic and serum proteome to identify and characterize complement protein signatures in severe AH (sAH). The quantity of multiple complement proteins was perturbed in liver and serum proteome of patients with sAH. Multiple complement proteins differentiated patients with sAH from those with alcohol cirrhosis (AC), alcohol use disorder (AUD) and healthy controls (HCs). Notably, serum collectin 11 and C1q binding protein were strongly associated with sAH and exhibited good discriminatory performance amongst patients with sAH, AC, AUD, and HCs. Furthermore, complement component receptor 1-like protein (CR1L) was negatively associated with pro-inflammatory cytokines. Additionally, lower serum mannose-binding lectin associated serine protease 1 and coagulation factor II were associated with and independently predicted 90-day mortality. In summary, meta-analysis of proteomic profiles from liver and circulation revealed complement protein signatures of sAH, highlighting a complex perturbation of complement and identifying potential diagnostic and prognostic biomarkers for patients with sAH.
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