宿主免疫和HBVS基因突变在HBsAg阴性HBV感染患者
Xin Liu1, Shu-Xiang Chen1, Hui Liu1
1Department of Clinical Laboratory Center, Beijing Youan Hospital, Capital Medical University, Beijing, China.
Frontiers in immunology
|August 30, 2023
概括
乙型肝炎病毒 (HBV) DNA 即使在HBsAg阴性后也可以持续存在,这表明T淋巴细胞子集的改变和免疫细胞因子激素的升高. 这些患者的HBV S基因突变可能会影响HBsAg检测和免疫反应.
科学领域:
- 肝病学和病毒学.
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 一些患者通过抗病毒疗法或自发地达到乙型肝炎表面抗原 (HBsAg) 的负性,但在血清中仍保留可检测的乙型肝炎病毒 (HBV) DNA.
- 在HBsAg阴性个体中持久的低水平HBVDNA表明病毒活动正在进行或改变了宿主-病原体相互作用.
- 了解这些患者的免疫和病毒学特征对于治疗慢性HBV感染至关重要.
研究的目的:
- 在HBsAg阴性但HBVDNA阳性的患者中,研究T淋巴细胞子集,血清细胞因子档案和HBVS基因序列.
- 将这些参数与持久HBsAg阳性患者和健康对照组的参数进行比较.
- 阐明HBsAg消极性背后的潜在机制,尽管HBVDNA持续存在.
主要方法:
- 流细胞计用于分析T淋巴细胞子集 (T%,CD8+,CD4+T淋巴细胞,CD4/CD8比率).
- 通过Luminex技术测量了血清中细胞因子和化学因子水平,包括IFN-γ,IFN-α,FLT-3L,IL-6,IL-8,IL-10,IL-12和IL-17A.
- 桑格测序用于分析HBV S基因区域的氨基酸替代和突变.
主要成果:
- 与健康对照组和HBsAg阳性患者相比,HBsAg阴性,HBVDNA阳性患者的T淋巴细胞百分比和计数 (CD8 +,CD4 +) 显著降低.
- 在HBsAg阴性患者中观察到IFN-γ,IFN-α和FLT-3L的血清水平升高,而促炎细胞因子 (IL-6,IL-8,IL-10,IL-12,IL-17A) 的水平较低.
- 在HBsAg阴性患者的HBV S基因中发现了高频氨基酸替代,包括免疫逃生突变 (例如Y100C,G145A) 和跨膜域替代.
结论:
- 患有HBsAg阴性,HBVDNA阳性的患者表现出明显的免疫特征,其特征是细胞免疫力受损,但潜在的肝炎可能减弱.
- 已识别的HBV S基因突变可能导致HBsAg无法检测,抗原性改变或病毒分泌受损,从而解释了血清学特征.
- 这些发现凸显了慢性HBV感染的复杂性,以及需要进行超越HBsAg状态的综合评估.
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