Department of Gastroenterology and Rheumatology, Section of Hepatology, University Hospital Leipzig, Leipzig, Germany.
Department of Gastroenterology, Hepatology and Diabetology, Internal Medicine II, HELIOS Hospital Emil von Behring, Berlin, Germany.
Sci Rep. 2018 Aug 24;8(1):12737. doi: 10.1038/s41598-018-31065-6.
Innate immunity can induce spontaneous hepatitis B surface antigen (HBsAg) seroclearance (SC) of hepatitis B virus (HBV) infection or transition towards an inactive carrier state. Toll-like receptor (TLR) 3 signalling has been linked to these processes. Alterations in the TLR3 gene might impair immune responses against HBV. In our study, we analysed the impact of the TLR3 polymorphisms rs3775291 and rs5743305 on the natural course of HBV infection. In this retrospective study, a Caucasian cohort of 621 patients with chronic HBV infection (CHB), 239 individuals with spontaneous HBsAg SC, and 254 healthy controls were enrolled. In the CHB group, 49% of patients were inactive carriers, and 17% were HBeAg-positive. The TLR3 rs3775291 A allele was associated with a reduced likelihood of spontaneous HBsAg SC and HBeAg SC, and an increased risk of developing chronic hepatitis B. In haplotype analysis, the haplotype including both risk variants rs3775291A and rs5743305A had the lowest likelihood of HBsAg SC. Further research in larger cohorts and functional analyses are needed to shed light on the impact of TLR3 signalling.
先天免疫可以诱导乙型肝炎病毒 (HBV) 感染的乙型肝炎表面抗原 (HBsAg) 自发性清除 (SC) 或向非活动携带状态转变。Toll 样受体 (TLR) 3 信号与这些过程有关。TLR3 基因的改变可能会损害针对 HBV 的免疫反应。在我们的研究中，我们分析了 TLR3 多态性 rs3775291 和 rs5743305 对 HBV 感染自然病程的影响。在这项回顾性研究中，我们招募了 621 名慢性 HBV 感染 (CHB) 患者、239 名自发性 HBsAg SC 患者和 254 名健康对照者的白种人队列。在 CHB 组中，49%的患者为非活动携带状态，17%的患者 HBeAg 阳性。TLR3 rs3775291 A 等位基因与自发性 HBsAg SC 和 HBeAg SC 的可能性降低以及发生慢性乙型肝炎的风险增加相关。在单倍型分析中，包含两个风险变异 rs3775291A 和 rs5743305A 的单倍型发生 HBsAg SC 的可能性最低。需要在更大的队列中进行进一步的研究和功能分析，以阐明 TLR3 信号的影响。
