Frontiers in Cellular and Infection Microbiology (Jul 2024)

Argonaute-2 autoantibodies: a promising biomarker for predicting mortality in HBV-related acute-on-chronic liver failure patients with cirrhosis

  • Yixuan Wang,
  • Yue Hu,
  • Jiaqi Li,
  • Huailu Ma,
  • Zongqi Shi,
  • Chaojing Wen,
  • Yu Long,
  • Ziwei Li,
  • Hang Sun,
  • Yixuan Yang,
  • Xiaofeng Shi

DOI
https://doi.org/10.3389/fcimb.2024.1407064
Journal volume & issue
Vol. 14

Abstract

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Background & aimsHBV 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.MethodWe 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.ResultsUtilizing 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.ConclusionsAGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.

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