乙型肝炎 e 抗原阴性慢性乙型肝炎患者乙型肝炎表面抗原自发血清转换的免疫相关性。
Immune correlates of hepatitis B surface antigen spontaneous seroconversion in hepatitis B e antigen negative chronic hepatitis B patients.
机构信息
Departments of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India.
Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India.
出版信息
Liver Int. 2018 Jan;38(1):38-49. doi: 10.1111/liv.13475. Epub 2017 Jun 1.
BACKGROUND
Hepatitis B surface antigen (HBsAg) seroconversion in HBeAg -ve chronic hepatitis B (CHB) infection is rare, possibly due to poor antigen processing and impaired humoral response. We investigated the role of dendritic cells (DCs), T follicular helper (TFH) cells and plasma B cells in seroconversion.
METHODS
HBeAg -ve (n=135) CHB patients with raised ALT at baseline were followed up. Patients undergoing HBsAg seroconversion (Gr. I, n=11) were compared with non-converters with low (Gr. II, n=17, HBV DNA<2000 IU/mL) or high HBV DNA (Gr. III, HBV DNA >2000 IU/mL, n=17). We measured cell phenotypes (TFH, B and DCs), HBV specific T-cell functionality [using pooled overlapping surface and core peptides], IL21 levels and gene expression analysis by qRT-PCR.
RESULTS
Patients in Gr. I compared to Gr. II and III, had higher IL-21 levels (865 vs 276 vs 111 pg/mL, P=<.0001), TFH (CD4 CXCR5 ) cells (12.3 vs 4.67 vs 2.77, P=<.001), inducible T-cell co-stimulator (ICOS) expression on TFH cells (20.0 vs 13.0 vs 13.68, P=.01), HBsAg specific IL-17 (9.40 vs 2.33 vs 2.61, P=<.001) and TNF-α secreting TFH17 cells (82 vs 1.43 vs 2.33, P=<.001), plasma B (CD19 CD38 ) cells (15.0 vs 5.08 vs 5.57, P=<.001), myeloid (17.80 vs 5.39 vs 2.70, P=<.001) and plasmocytoid DCs (2.6 vs 0.43 vs 0.21, P=<.001). Plasma B-cell frequency (R =.64, P=.01) and IL-21 levels (R =.52, P=.003) correlated with anti-HBs titres in patients with HBsAg seroconversion.
CONCLUSIONS
Dendritic cell and TFH cell mediated responses regulate humoral responses against HBV and play a major role in HBsAg seroconversion in CHB patients.
背景
乙型肝炎表面抗原（HBsAg）在 HBeAg-阴性慢性乙型肝炎（CHB）感染中的血清转换较为罕见，这可能是由于抗原加工不良和体液免疫反应受损所致。我们研究了树突状细胞（DC）、滤泡辅助性 T（TFH）细胞和浆细胞在血清转换中的作用。
方法
我们对基线时 ALT 升高的 HBeAg-阴性（n=135）CHB 患者进行了随访。将发生 HBsAg 血清转换（Gr. I，n=11）的患者与低 HBV DNA（Gr. II，n=17，HBV DNA<2000 IU/mL）或高 HBV DNA（Gr. III，HBV DNA >2000 IU/mL，n=17）的未转换患者进行比较。我们通过 qRT-PCR 检测了细胞表型（TFH、B 和 DC）、HBV 特异性 T 细胞功能[使用重叠的表面和核心肽段的池]、IL21 水平和基因表达分析。
结果
与 Gr. II 和 III 相比，Gr. I 组患者的 IL-21 水平（865 vs 276 vs 111 pg/mL，P<.0001）、TFH（CD4 CXCR5）细胞（12.3 vs 4.67 vs 2.77，P<.001）、TFH 细胞上诱导型 T 细胞共刺激因子（ICOS）表达（20.0 vs 13.0 vs 13.68，P=.01）、HBsAg 特异性 IL-17（9.40 vs 2.33 vs 2.61，P<.001）和 TNF-α分泌 TFH17 细胞（82 vs 1.43 vs 2.33，P<.001）、浆细胞（CD19 CD38）（15.0 vs 5.08 vs 5.57，P<.001）、髓样（17.80 vs 5.39 vs 2.70，P<.001）和浆细胞样 DC（2.6 vs 0.43 vs 0.21，P<.001）水平较高。HBsAg 血清转换患者中，浆细胞频率（R =.64，P=.01）和 IL-21 水平（R =.52，P=.003）与抗-HBs 滴度相关。
结论
树突状细胞和 TFH 细胞介导的反应调节针对乙型肝炎病毒的体液免疫反应，并在 CHB 患者的 HBsAg 血清转换中起主要作用。
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