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Abstract Details
Auto-antibodies against interferons are common in people living with chronic hepatitis B virus infection and associate with PegIFN? non-response.
Fink, Douglas L (DL);Etoori, David (D);Hill, Robert (R);Idilli, Orest (O);Kartikapallil, Nikita (N);Payne, Olivia (O);Griffith, Sarah (S);Bradford, Hannah F (HF);Mauri, Claudia (C);Kennedy, Patrick T F (PTF);McCoy, Laura E (LE);Maini, Mala K (MK);Gill, Upkar S (US);
BACKGROUND & 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 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 patients with CHB had any detectable anti-IFN auto-Abs at any time and 6.5% (18/276) anti-T3IFN auto-Abs, with a high incidence of PegIFNα-induced auto-Abs (31.4%, 11/35). However, only a minority of auto-Ab-positive sera demonstrated neutralisation (4/46, 8.7%). Auto-Ab positivity correlated with higher median HBsAg levels ( = 0.0110). All individuals with detectable anti-T1IFN auto-Abs were PegIFNα 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-Abs in CHB are required to characterise the association with long-term outcomes.
IMPACT AND IMPLICATIONS: HBV and PegIFNα individually may induce broad autoreactivity associated with dysregulated antiviral immune responses. Auto-Ab screening prior to PegIFNα treatment or other immunotherapies may play a critical role in predicting treatment responses.
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