Auto-antibodies against interferons are common in people living with chronic hepatitis B virus infection and associate with PegIFN non-response
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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, 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 α -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 α non-responders including those without auto-Ab against IFN α specifically.
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 α individually may induce broad auto-reactivity associated with dysregulated anti-viral immune responses. Auto-Ab screening pre-PegIFN α and other immunotherapies may have a critical role in stratifying patient selection.
