Association among cytokine profiles of innate and adaptive immune responses and clinical-virological features in untreated patients with chronic hepatitis B
Association among cytokine profiles of innate and adaptive immune responses and clinical-virological features in untreated patients with chronic hepatitis B
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DOI：
10.1186/s12879-020-05233-x
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发表时间：
2020-07-14
影响因子：
3.7
通讯作者：
Huang, Yuehua
中科院分区：
文献类型：
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作者：
Gu, Yurong;Lian, Yifan;Huang, Yuehua
细胞内病毒的完全清除依赖于先天免疫系统和适应性免疫系统的效应细胞。本研究旨在确定自然杀伤细胞（NK）和T细胞产生的抗病毒细胞因子与未经治疗的慢性乙型肝炎（CHB）患者临床病毒学特征之间的关系。方法在慢性乙型肝炎病毒（HBV）感染（CHB）队列中，我们分别测量了T、NK和自然杀伤T （NKT）细胞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)和白细胞介素-2 （IL-2）。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联系起来。结果ifn - γ(+)和tnf - α (+)CD4（+）和CD8(+)T细胞水平在免疫活性（IA）期明显高于其他期。免疫耐受（IT）患者NK细胞和NKT细胞表达ifn - γ最低，NK细胞表达tnf - α最低。ifn - γ(+)、tnf - α(+)和IL-2(+)CD4（+）和CD8(+)T细胞频率在IA期和灰色区（GZ）期相似。基于细胞因子的主成分分析证实，大多数IT患者与非活性携带者（IC）和IA患者差异显著，而GZ患者分布广泛。多变量分析显示，T和NK细胞产生ifn - γ和tnf - α，但不产生IL-2，与血清丙氨酸转氨酶（ALT）有显著相关性。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临床分期具有不同的细胞因子特征，这与未经治疗的CHB患者的病毒特征有关。
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-gamma), tumor necrosis factor-alpha (TNF-alpha), 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-gamma(+)and TNF-alpha(+)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-gamma by NK and NKT cells, and TNF-alpha by NK cells. IFN-gamma(+), TNF-alpha(+)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-gamma and TNF-alpha, but not IL-2, had significant association with serum alanine aminotransferase (ALT). Moreover, IFN-gamma+NKT cells were associated with HBV DNA, while IFN-gamma(+)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.