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bioRxiv · 10.1101/2024.09.24.614789

Auto-antibodies against interferons are common in people living with chronic hepatitis B virus infection and associate with PegIFN non-response

Fink, D. L.·Etoori, D.·Hill, R.·Idilli, O.·Kartikapallil, N.·Payne, O.·Griffith, S.·Bradford, H.·Mauri, C.·Kennedy, P. T. F.·McCoy, L. E.·Maini, M. K.·Gill, U. S.
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Abstract

Background and aimsType 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. MethodsOur 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. ResultsOverall, 11.9% (33/276) of CHB patients had any detectable anti-IFN auto-Abs and 9.8% (27/276) anti-T3IFN auto-Abs, with high incidence of PegIFN-induced de novo auto-Ab (25.7%, 9/35). However, only a minority of auto-Ab-positive sera demonstrated neutralisation in vitro (3/33, 9.1%). Auto-Ab-positivity correlated with higher median HBsAg levels (p=0.0024). All individuals with detectable auto-Ab were PegIFN non-responders including those without auto-Ab against IFN specifically. ConclusionsNon-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 implicationsHBV 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.

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Fink, D. L., Etoori, D., Hill, R., Idilli, O., Kartikapallil, N., Payne, O., Griffith, S., Bradford, H., Mauri, C., Kennedy, P. T. F., McCoy, L. E., Maini, M. K., Gill, U. S.. 2024-09-25. Auto-antibodies against interferons are common in people living with chronic hepatitis B virus infection and associate with PegIFN non-response. https://doi.org/10.1101/2024.09.24.614789

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