Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd., Guangzhou, 510630, China.
Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
BMC Infect Dis. 2019 Mar 4;19(1):216. doi: 10.1186/s12879-019-3853-2.
Hepatitis B virus (HBV) replicates non-cytopathically in the hepatocytes and HBV-related diseases are caused by immune-mediated inflammatory events. This study aimed to identify the relationship between clinical-virological characteristics and immunity in untreated chronic hepatitis B (CHB) patients.
A total of 209 CHB patients were categorized into immune tolerant (IT, n = 17), inactive carrier (IC, n = 20), immune active (IA, n = 120), and gray zone (GZ, n = 72) phases. The quantitative hepatitis B surface antigen (qHBsAg), hepatitis B e antigen (HBeAg), anti-HBeAg (HBeAb), HBV genotype, viral mutant and frequencies of interleukin (IL)-4, IL-17, IL-10 and interferon-gamma (IFN-γ) produced by CD4 and CD8 T cells were tested. We also correlated these cytokines with clinical-virological characteristics using a linear regression model.
CD8 T cells frequency were significantly decreased in IT patients. Levels of CD4 T cells IL-4 or IL-10 were strongly negatively associated with qHBsAg titers. The frequency of IFN-γ produced by CD4 and CD8 T cells showed significant positive association with age and alanine aminotransferase (ALT) level, while that had negative association with qHBsAg titers. Additionally, the ratios of mutations in the HBV precore (PC) stop codon and basal core promoter (BCP) and the combined mutations were 32.5, 27.2, and 11.3%, respectively. The frequency of CD4 T cells IL-17 was higher in patients with a PC mutation than that in patients carrying a wild-type sequence. Finally, little associations among T cell derived IL-4, IL-10, IL-17, and IFN-γ was observed in the current untreated CHB cohort.
Several components of the immune system were correlated with HBV factors that influence an inflammatory process during CHB. Of particular relevance are the significant associations of between CD4 T cells IL-4 and qHBsAg level, and between CD4 T cells IL-17 and the presence of a mutation in PC.
乙型肝炎病毒（HBV）在肝细胞中非细胞病变复制，HBV 相关疾病是由免疫介导的炎症事件引起的。本研究旨在确定未经治疗的慢性乙型肝炎（CHB）患者的临床病毒学特征与免疫之间的关系。
共纳入 209 例 CHB 患者，分为免疫耐受（IT）期（n=17）、非活动携带（IC）期（n=20）、免疫激活（IA）期（n=120）和灰色区（GZ）期（n=72）。检测定量乙型肝炎表面抗原（qHBsAg）、乙型肝炎 e 抗原（HBeAg）、抗-HBeAg（HBeAb）、HBV 基因型、病毒突变以及 CD4 和 CD8 T 细胞产生的白细胞介素（IL）-4、IL-17、IL-10 和干扰素-γ（IFN-γ）的频率。我们还使用线性回归模型将这些细胞因子与临床病毒学特征相关联。
IT 期患者的 CD8 T 细胞频率明显降低。CD4 T 细胞 IL-4 或 IL-10 水平与 qHBsAg 滴度呈强烈负相关。CD4 和 CD8 T 细胞产生的 IFN-γ频率与年龄和丙氨酸氨基转移酶（ALT）水平呈显著正相关，而与 qHBsAg 滴度呈负相关。此外，HBV 前核心（PC）终止密码子和基本核心启动子（BCP）突变以及联合突变的比率分别为 32.5%、27.2%和 11.3%。PC 突变患者的 CD4 T 细胞 IL-17 频率高于野生型序列患者。最后，在未经治疗的 CHB 队列中，观察到 T 细胞衍生的 IL-4、IL-10、IL-17 和 IFN-γ 之间几乎没有关联。
免疫系统的几个组成部分与影响 CHB 炎症过程的 HBV 因素相关。特别相关的是 CD4 T 细胞 IL-4 与 qHBsAg 水平之间以及 CD4 T 细胞 IL-17 与 PC 突变之间的显著关联。
