Fink, DL;
Etoori, D;
Hill, R;
Idilli, O;
Kartikapallil, N;
Payne, O;
Griffith, S;
... Gill, US; + view all
(2025)
Auto-antibodies against interferons are common in people living with chronic hepatitis B virus infection and associate with PegIFN non-response.
JHEP Reports
, Article 101382. 10.1016/j.jhepr.2025.101382.
(In press).
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Abstract
Background and aims: Type one (T1) and three interferons (T3IFNs) are implicated in Chronic Hepatitis B (CHB) immunopathogenesis. IFN remains the only licenced immune modulating therapy for CHB. We measured the prevalence of auto-antibodies (auto-Abs) against T1 and T3IFNs to examine the hypothesis that they impact Hepatitis B Virus (HBV) control and treatment response, as highlighted by COVID-19. Methods: Our multi-centre retrospective longitudinal study accessed two CHB cohorts, auto-Ab levels and neutralisation status were measured against T1IFN and T3IFN. Associations were tested against HBV clinical parameters. Results: Overall, 16.7% (46/276) of CHB patients had any detectable anti-IFN auto-Abs at any time and 6.5% (18/276) anti-T3IFN auto-Abs, with high incidence of PegIFN -induced de novo auto-Ab (31.4%, 11/35). However, only a minority of auto-Ab-positive sera demonstrated neutralisation in vitro (4/46, 8.7%). Auto-Ab-positivity correlated with higher median HBsAg levels (p=0.0110). All individuals with detectable anti-T1IFN auto-Abs were PegIFN non-responders. Conclusions: Non-neutralising anti-IFN auto-Abs are common in CHB and associate with higher median HBsAg levels. Further prospective study of anti-cytokine auto-Ab in CHB are required to characterise association with long-term outcomes. Impact and implications: HBV and PegIFN individually may induce broad auto-reactivity associated with dysregulated anti-viral immune responses. Auto-Ab screening pre-PegIFN and other immunotherapies may have a critical role in stratifying patient selection.
| Type: | Article |
|---|---|
| Title: | Auto-antibodies against interferons are common in people living with chronic hepatitis B virus infection and associate with PegIFN non-response |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.jhepr.2025.101382 |
| Publisher version: | https://doi.org/10.1016/j.jhepr.2025.101382 |
| Language: | English |
| Additional information: | This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | chronic hepatitis B, CHB, interferon, auto-antibodies |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10206478 |
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