未经治疗的慢性乙型肝炎患者先天性和适应性免疫应答的细

StephenW

Association among cytokine profiles of innate and adaptive immune responses and clinical-virological features in untreated patients with chronic hepatitis B
Yurong Gu  1 , Yifan Lian  2 , Qiaolan Zheng  3 , Zexuan Huang  2 , Lin Gu  2 , Yanhua Bi  2 , Jing Li  2 , Yanlin Huang  1 , Yuankai Wu  1 , Lubiao Chen  4 , Yuehua Huang  5   6
Affiliations
Affiliations

    1
    Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd, Guangzhou, 510630, China.
    2
    Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd, Guangzhou, 510630, China.
    3
    Journal Center, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd, Guangzhou, 510630, China.
    4
    Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd, Guangzhou, 510630, China. [email protected].
    5
    Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd, Guangzhou, 510630, China. [email protected].
    6
    Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tian He Rd, Guangzhou, 510630, China. [email protected].

    PMID: 32664850 DOI: 10.1186/s12879-020-05233-x

Abstract

Background: Complete clearance of intracellular viruses depends on effector cells of innate and adaptive immune systems. This study aimed to identify the relationships among antiviral cytokines produced by natural killer (NK) and T cells and clinical-virological characteristics in untreated chronic hepatitis B (CHB) patients.

Methods: We measured antiviral cytokines interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) produced by T, NK and natural killer T (NKT) cells, respectively, in a cohort with chronic hepatitis B virus (HBV) infection (CHB). We also correlated these cytokines with clinical-virological characteristics using a linear regression model.

Results: levels of IFN-γ+ and TNF-α+ CD4+ and CD8+ T cells were significantly higher in immune active (IA) phase than in other phases. Immune tolerant (IT) patients showed the lowest expression of IFN-γ by NK and NKT cells, and TNF-α by NK cells. IFN-γ+, TNF-α+ and IL-2+ CD4+ and CD8+ T cells frequencies were similar between IA and gray zone (GZ) phases. Principal component analysis based on cytokines confirmed that most IT patients significantly differed from inactive carriers (IC) and IA patients, while GZ patients were widely scattered. Multivariate analysis showed both T and NK cells producing IFN-γ and TNF-α, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-γ+ NKT cells were associated with HBV DNA, while IFN-γ+ CD4+ and CD8+ T cells were correlated with age.

Conclusion: HBV clinical phases are characterized by distinct cytokine signatures, which showed relationship to viral features in these untreated CHB patients.

Keywords: Adaptive immunity; Chronic hepatitis B (CHB); Cytokines; Innate immunity; Regression analysis.

StephenW

未经治疗的慢性乙型肝炎患者先天性和适应性免疫应答的细胞因子谱与临床病毒学特征之间的关联
顾玉荣1，一凡联2，郑巧兰3，黄宣萱2，林谷2，颜华碧2，景丽2，颜艳琳1，吴远开1，陈陆标4，黄月华5 6
隶属关系
隶属关系

    1个
    中山大学附属第三医院传染病科，广东广州天河路600号，510630
    2
    中山大学附属第三医院广东省肝病研究重点实验室，广州市天河路600号，510630
    3
    中山大学附属第三医院新闻中心，广州天河路600号，510630
    4
    中山大学附属第三医院传染病科，广东广州天河路600号，510630 [email protected]。
    5
    中山大学附属第三医院传染病科，广东广州天河路600号，510630 [email protected]。
    6
    中山大学附属第三医院广东省肝病研究重点实验室，广州市天河路600号，510630 [email protected]。

    PMID：32664850 DOI：10.1186 / s12879-020-05233-x

抽象

背景：细胞内病毒的完全清除取决于先天和适应性免疫系统的效应细胞。这项研究旨在确定未经治疗的慢性乙型肝炎（CHB）患者的自然杀伤（NK）和T细胞产生的抗病毒细胞因子与临床病毒学特征之间的关系。

方法：我们分别测量了由T细胞，NK细胞和自然杀伤性T细胞（NKT）产生的抗病毒细胞因子干扰素-γ（IFN-γ），肿瘤坏死因子-α（TNF-α）和白介素2（IL-2）。 ，患有慢性乙型肝炎病毒（HBV）感染（CHB）的队列中。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。

结果：免疫活性（IA）阶段的IFN-γ+和TNF-α+ CD4 +和CD8 + T细胞水平显着高于其他阶段。免疫耐受（IT）患者的NK和NKT细胞的IFN-γ表达最低，而NK细胞的TNF-α最低。 IA和灰区（GZ）期之间的IFN-γ+，TNF-α+和IL-2 + CD4 +和CD8 + T细胞频率相似。基于细胞因子的主成分分析证实，大多数IT患者与非活动携带者（IC）和IA患者存在显着差异，而GZ患者则散布在各处。多变量分析显示，产生IFN-γ和TNF-α的T细胞和NK细胞均与血清丙氨酸氨基转移酶（ALT）显着相关，而IL-2没有。此外，IFN-γ+ NKT细胞与HBV DNA相关，而IFN-γ+ CD4 +和CD8 + T细胞与年龄相关。

结论：HBV临床阶段的特征在于明显的细胞因子特征，这些特征与这些未经治疗的CHB患者的病毒特征有关。

关键词：适应性免疫；慢性乙型肝炎（CHB）；细胞因子；先天免疫;回归分析。

StephenW

https://bmcinfectdis.biomedcentr ... /s12879-020-05233-x