Fink Douglas L, Etoori David, Hill Robert, Idilli Orest, Kartikapallil Nikita, Payne Olivia, Griffith Sarah, Bradford Hannah F, Mauri Claudia, Kennedy Patrick T F, McCoy Laura E, Maini Mala K, Gill Upkar S
Infection and Immunity, University College London, London, UK.
Royal Free London NHS Foundation Trust, London, UK.
JHEP Rep. 2025 Feb 28;7(5):101382. doi: 10.1016/j.jhepr.2025.101382. eCollection 2025 May.
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.
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.
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.
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.
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.
I型（T1）和III型干扰素（T3IFNs）与慢性乙型肝炎（CHB）的免疫发病机制有关。干扰素仍然是唯一获得许可用于CHB的免疫调节疗法。我们测量了针对T1和T3IFNs的自身抗体（自身抗体）的流行率，以检验它们影响HBV控制和治疗反应的假设，如COVID-19所强调的那样。
我们的多中心回顾性纵向研究纳入了两个CHB队列；测量了针对T1IFN和T3IFN的自身抗体水平和中和状态。测试了与HBV临床参数的相关性。
总体而言，16.7%（46/276）的CHB患者在任何时候都有可检测到的抗干扰素自身抗体，6.5%（18/276）有抗T3IFN自身抗体，聚乙二醇干扰素α诱导的自身抗体发生率很高（31.4%，11/35）。然而，只有少数自身抗体阳性血清表现出中和作用（4/46，8.7%）。自身抗体阳性与较高的HBsAg中位数水平相关（P = 0.0110）。所有可检测到抗T1IFN自身抗体的个体都是聚乙二醇干扰素α无反应者。
非中和性抗干扰素自身抗体在CHB中很常见，并且与较高的HBsAg中位数水平相关。需要对CHB中的抗细胞因子自身抗体进行进一步的前瞻性研究，以确定其与长期结局的关联。
HBV和聚乙二醇干扰素α单独可能诱导与抗病毒免疫反应失调相关的广泛自身反应性。在聚乙二醇干扰素α治疗或其他免疫治疗之前进行自身抗体筛查可能在预测治疗反应中起关键作用。
