Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Department of Vascular Surgery, Chongqing Medical University, Chongqing, China.
Front Cell Infect Microbiol. 2024 Jul 25;14:1407064. doi: 10.3389/fcimb.2024.1407064. eCollection 2024.
BACKGROUND & AIMS: 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.
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.
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.
AGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.
HBV 感染引发自身免疫反应，导致自身抗体产生。本研究探讨了自身抗体在 HBV 相关慢加急性肝衰竭（ACLF）中的作用，为临床管理提供了新视角。
我们应用免疫沉淀和 iTRAQ 技术筛选 HBV 相关肝硬化患者血清中的自身抗体，并在 238 例 HBV 感染个体和 49 例健康对照中进行构象稳定 ELISA 检测。我们的结果在包含 106 例 ACLF 患者的回顾性队列中得到验证，并通过另外 10 例 ACLF 病例的肝组织免疫组化分析进行了进一步评估。
利用 iTRAQ，我们在本研究中鉴定出 Argonaute1-3 自身抗体（AGO-Abs）。AGO2-Abs 在肝硬化、失代偿和进一步的 ACLF 中显著增加，而 AGO1-Abs 和 AGO3-Abs 则不然。这反映了疾病严重程度的相关性。逻辑回归和 COX 模型证实 AGO2-Abs 是失代偿性肝硬化（DLC）和 ACLF 的独立预后指标。在 ROC 分析中，AGO2-Abs 对预测 28 天和 90 天死亡率具有显著的诊断价值（AUROC = 0.853 和 0.854）。此外，将 AGO2-Abs 与 Child-Pugh、MELD 和 AARC 评分相结合，显著提高了它们的预测准确性（P < 0.05）。Kaplan-Meier 分析表明，AGO2-Abs 水平高于 99.14μg/ml 时生存较差。这些发现得到了回顾性验证队列的支持。此外，免疫组化显示门脉周围肝区存在带状 AGO2 表达，AGO2-Abs 水平与总胆红素相关，表明其可能通过门脉周围功能加剧肝损伤。
AGO2-Abs 是预测 HBV 相关 ACLF 患者死亡率的强有力生物标志物。
