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Type 1 interferon auto-antibodies are elevated in patients with decompensated liver cirrhosis.

Authors
  • Greville, Gordon1
  • Cremen, Sinead2
  • O'Neill, Shauna1
  • Azarian, Sarah1
  • Brady, Gareth3
  • McCormack, William3
  • Dyer, Adam H4
  • Bourke, Nollaig M4
  • Touzelet, Olivier5
  • Courtney, David5
  • Power, Ultan F5
  • Dowling, Paul1
  • Gallagher, Tom K6
  • Bamford, Connor G G5, 7
  • Robinson, Mark W1
  • 1 Department of Biology, Kathleen Lonsdale Institute for Human Health Research, Maynooth University, Maynooth, Ireland. , (Ireland)
  • 2 School of Medicine, University College Dublin, Dublin, Ireland. , (Ireland)
  • 3 Discipline of Clinical Medicine, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland. , (Ireland)
  • 4 Discipline of Medical Gerontology, School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland. , (Ireland)
  • 5 Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, Northern Ireland. , (Ireland)
  • 6 Department of Hepatopancreaticobiliary and Transplant Surgery, St. Vincent's University Hospital, Dublin, Ireland. , (Ireland)
  • 7 School of Biological Sciences and Institute for Global Food Security (IGFS), Queen's University Belfast, Belfast, Northern Ireland. , (Ireland)
Type
Published Article
Journal
Clinical & Experimental Immunology
Publisher
Wiley (Blackwell Publishing)
Publication Date
Feb 07, 2024
Volume
215
Issue
2
Pages
177–189
Identifiers
DOI: 10.1093/cei/uxad119
PMID: 37917972
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Patients with decompensated liver cirrhosis, in particular those classified as Childs-Pugh class C, are at increased risk of severe coronavirus disease-2019 (COVID-19) upon infection with severe acute respiratory coronavirus 2 (SARS-CoV-2). The biological mechanisms underlying this are unknown. We aimed to examine the levels of serum intrinsic antiviral proteins as well as alterations in the innate antiviral immune response in patients with decompensated liver cirrhosis. Serum from 53 SARS-CoV-2 unexposed and unvaccinated individuals, with decompensated liver cirrhosis undergoing assessment for liver transplantation, were screened using SARS-CoV-2 pseudoparticle and SARS-CoV-2 virus assays. The ability of serum to inhibit interferon (IFN) signalling was assessed using a cell-based reporter assay. Severity of liver disease was assessed using two clinical scoring systems, the Child-Pugh class and the MELD-Na score. In the presence of serum from SARS-CoV-2 unexposed patients with decompensated liver cirrhosis there was no association between SARS-CoV-2 pseudoparticle infection or live SARS-CoV-2 virus infection and severity of liver disease. Type I IFNs are a key component of the innate antiviral response. Serum from patients with decompensated liver cirrhosis contained elevated levels of auto-antibodies capable of binding IFN-α2b compared to healthy controls. High MELD-Na scores were associated with the ability of these auto-antibodies to neutralize type I IFN signalling by IFN-α2b but not IFN-β1a. Our results demonstrate that neutralizing auto-antibodies targeting IFN-α2b are increased in patients with high MELD-Na scores. The presence of neutralizing type I IFN-specific auto-antibodies may increase the likelihood of viral infections, including severe COVID-19, in patients with decompensated liver cirrhosis. © The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology.

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