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

Front Cell Infect Microbiol. 2024 Jul 25:14:1407064. doi: 10.3389/fcimb.2024.1407064. eCollection 2024.

Abstract

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.

Method: 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.

Results: 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.

Conclusions: AGO2-Abs is a robust biomarker for predicting the mortality of patients with HBV-related ACLF.

Keywords: acute-on-chronic liver failure; argonaute-2 autoantibodies; chronic hepatitis B; mortality; predictive biomarker.

MeSH terms

  • Acute-On-Chronic Liver Failure* / immunology
  • Acute-On-Chronic Liver Failure* / mortality
  • Adult
  • Argonaute Proteins*
  • Autoantibodies* / blood
  • Autoantibodies* / immunology
  • Biomarkers* / blood
  • Female
  • Hepatitis B, Chronic / complications
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / mortality
  • Humans
  • Liver / pathology
  • Liver Cirrhosis* / immunology
  • Liver Cirrhosis* / mortality
  • Male
  • Middle Aged
  • Prognosis
  • ROC Curve
  • Retrospective Studies

Substances

  • AGO2 protein, human
  • Argonaute Proteins
  • Autoantibodies
  • Biomarkers

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a Remarkable Innovation-Clinical Research Project and the DengFeng Program of the Second Affiliated Hospital of Chongqing Medical University (No. 472020320230023).