PDF(Pubmed)
Abstract：
UNASSIGNED: HBV infection initiates autoimmune responses, leading to autoantibody generation. This research explores the role of autoantibodies in HBV-related Acute-on-Chronic Liver Failure (ACLF), offering novel perspectives for clinical management.
UNASSIGNED: We applied immunoprecipitation and iTRAQ techniques to screen for autoantibodies in serum from HBV-related cirrhosis patients and conducted detection with conformation- stabilizing ELISA in a cohort of 238 HBV-infected individuals and 49 health controls. Our results were validated in a retrospective cohort comprising 106 ACLF patients and further assessed through immunohistochemical analysis in liver tissues from an additional 10 ACLF cases.
UNASSIGNED: Utilizing iTRAQ, we identified Argonaute1-3 autoantibodies (AGO-Abs) in this research. AGO2-Abs notably increased in cirrhosis, decompensation, and further in ACLF, unlike AGO1-Abs and AGO3-Abs. This reflects disease severity correlation. Logistic regression and COX models confirmed AGO2-Abs as independent prognostic indicators for decompensated liver cirrhosis (DLC) and ACLF. In the ROC analysis, AGO2-Abs showed significant diagnostic value for predicting 28- and 90-day mortality (AUROC = 0.853 and 0.854, respectively). Furthermore, combining AGO2-Abs with the Child-Pugh, MELD, and AARC scores significantly improved their predictive accuracy (P < 0.05). Kaplan-Meier analysis showed poorer survival for AGO2-Abs levels above 99.14μg/ml. These findings were supported by a retrospective validation cohort. Additionally, immunohistochemistry revealed band-like AGO2 expression in periportal liver areas, with AGO2-Abs levels correlating with total bilirubin, indicating a potential role in exacerbating liver damage through periportal functions.
UNASSIGNED: AGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.
UNASSIGNED: We applied immunoprecipitation and iTRAQ techniques to screen for autoantibodies in serum from HBV-related cirrhosis patients and conducted detection with conformation- stabilizing ELISA in a cohort of 238 HBV-infected individuals and 49 health controls. Our results were validated in a retrospective cohort comprising 106 ACLF patients and further assessed through immunohistochemical analysis in liver tissues from an additional 10 ACLF cases.
UNASSIGNED: Utilizing iTRAQ, we identified Argonaute1-3 autoantibodies (AGO-Abs) in this research. AGO2-Abs notably increased in cirrhosis, decompensation, and further in ACLF, unlike AGO1-Abs and AGO3-Abs. This reflects disease severity correlation. Logistic regression and COX models confirmed AGO2-Abs as independent prognostic indicators for decompensated liver cirrhosis (DLC) and ACLF. In the ROC analysis, AGO2-Abs showed significant diagnostic value for predicting 28- and 90-day mortality (AUROC = 0.853 and 0.854, respectively). Furthermore, combining AGO2-Abs with the Child-Pugh, MELD, and AARC scores significantly improved their predictive accuracy (P < 0.05). Kaplan-Meier analysis showed poorer survival for AGO2-Abs levels above 99.14μg/ml. These findings were supported by a retrospective validation cohort. Additionally, immunohistochemistry revealed band-like AGO2 expression in periportal liver areas, with AGO2-Abs levels correlating with total bilirubin, indicating a potential role in exacerbating liver damage through periportal functions.
UNASSIGNED: AGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.
摘要：
■HBV感染启动自身免疫反应，导致自身抗体的产生。本研究探讨了自身抗体在HBV相关的急性对慢性肝衰竭（ACLF），为临床管理提供新的视角。
■我们应用免疫沉淀和iTRAQ技术来筛选HBV相关肝硬化患者血清中的自身抗体，并在238名HBV感染个体和49名健康对照人群中进行构象稳定ELISA检测。我们的结果在包括106名ACLF患者的回顾性队列中得到验证，并通过对另外10例ACLF病例的肝组织进行免疫组织化学分析进一步评估。
■利用iTRAQ，我们在这项研究中鉴定了Argonaute1-3自身抗体(AGO-Abs).AGO2-Ab在肝硬化中显著增加，代偿失调,在ACLF中，与AGO1-Abs和AGO3-Abs不同。这反映了疾病严重程度的相关性。Logistic回归和COX模型证实AGO2-Abs是失代偿期肝硬化（DLC）和ACLF的独立预后指标。在ROC分析中，AGO2-Ab对预测28天和90天死亡率显示出显著的诊断价值(AUROC分别为0.853和0.854)。此外，将AGO2-Abs与Child-Pugh相结合，MELD,AARC评分显著提高其预测准确性(P<0.05)。Kaplan-Meier分析显示AGO2-Abs水平高于99.14μg/ml时存活较差。这些发现得到了回顾性验证队列的支持。此外,免疫组织化学显示门静脉周围肝脏区域的带状AGO2表达，AGO2-Abs水平与总胆红素相关，表明通过门静脉功能加重肝损伤的潜在作用。
■AGO2-Abs是预测HBV相关ACLF患者死亡率的强大生物标志物。
■我们应用免疫沉淀和iTRAQ技术来筛选HBV相关肝硬化患者血清中的自身抗体，并在238名HBV感染个体和49名健康对照人群中进行构象稳定ELISA检测。我们的结果在包括106名ACLF患者的回顾性队列中得到验证，并通过对另外10例ACLF病例的肝组织进行免疫组织化学分析进一步评估。
■利用iTRAQ，我们在这项研究中鉴定了Argonaute1-3自身抗体(AGO-Abs).AGO2-Ab在肝硬化中显著增加，代偿失调,在ACLF中，与AGO1-Abs和AGO3-Abs不同。这反映了疾病严重程度的相关性。Logistic回归和COX模型证实AGO2-Abs是失代偿期肝硬化（DLC）和ACLF的独立预后指标。在ROC分析中，AGO2-Ab对预测28天和90天死亡率显示出显著的诊断价值(AUROC分别为0.853和0.854)。此外，将AGO2-Abs与Child-Pugh相结合，MELD,AARC评分显著提高其预测准确性(P<0.05)。Kaplan-Meier分析显示AGO2-Abs水平高于99.14μg/ml时存活较差。这些发现得到了回顾性验证队列的支持。此外,免疫组织化学显示门静脉周围肝脏区域的带状AGO2表达，AGO2-Abs水平与总胆红素相关，表明通过门静脉功能加重肝损伤的潜在作用。
■AGO2-Abs是预测HBV相关ACLF患者死亡率的强大生物标志物。
