贝叶斯细胞因子和趋化因子分析确定了慢性乙型肝炎治疗期

StephenW

Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment
Sriram Narayanan  1 , Veonice Bijin Au  1 , Atefeh Khakpoor  2 , Cheng Yan  2 , Patricia J Ahl  1 , Nivashini Kaliaperumal  1 , Bernett Lee  3 , Wen Wei Xiang  4 , Juling Wang  2 , Chris Lee  2 , Amy Tay  2 , Seng Gee Lim  1   2 , John E Connolly  5   6   7
Affiliations
Affiliations

    1
    Translational Immunology Programme, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research, Singapore (A*STAR) Research Entities (RE), 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore.
    2
    Division of Gastroenterology and Hepatology, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
    3
    Singapore Immunology Network, A*STAR REs, Singapore, Singapore.
    4
    IMCB, Tessa Therapeutics Pvt Ltd, Singapore, Singapore.
    5
    Translational Immunology Programme, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology, and Research, Singapore (A*STAR) Research Entities (RE), 61 Biopolis Drive, Proteos, Singapore, 138673, Singapore. [email protected].
    6
    Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. [email protected].
    7
    Institute of Biomedical Studies, Baylor University, Waco, TX, USA. [email protected].

    PMID: 33811250 DOI: 10.1038/s41598-021-86836-5

Abstract

Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side analogue-treated patients who achieved HBsAg loss with peg-interferon-α(peg-IFN-α) add-on or switch treatment in a randomised clinical trial. Cytokines/chemokines from plasma were compared between those with/without HBsAg loss, at baseline, before and after HBsAg loss. Peg-IFN-α treatment resulted in higher levels of IL-27, IL-12p70, IL-18, IL-13, IL-4, IL-22 and GM-CSF prior to HBsAg loss. Probabilistic network analysis of cytokines, chemokines and soluble factors suggested a dynamic dendritic cell driven NK and T cell immune response associated with HBsAg loss. Bayesian network analysis showed a dominant myeloid-driven type 1 inflammatory response with a MIG and I-TAC central module contributing to HBsAg loss in the add-on arm. In the switch arm, HBsAg loss was associated with a T cell activation module exemplified by high levels of CD40L suggesting T cell activation. Our findings show that more than one immune pathway to HBsAg loss was found with peg-IFN-α therapy; by myeloid-driven Type 1 response in one instance, and T cell activation in the other.

StephenW

贝叶斯细胞因子和趋化因子分析确定了慢性乙型肝炎治疗期间HBsAg丢失的免疫途径
Sriram Narayanan 1，Veonice Bijin Au 1，Atefeh Khakpoor 2，Cheng Yan 2，Patricia J Ahl 1，Nivashini Kaliaperumal 1，Bernett Lee 3，Wen Wei Xiang 4，Juling Wang 2，Chris Chris Lee 2，Amy Tay 2，Seng Gee Lim 1 2，约翰·E·康诺利5 6 7
隶属关系
隶属关系

    1个
    新加坡科学技术研究局分子与细胞生物学研究所（IMCB）的转化免疫学计划（A * STAR）研究实体（RE），新加坡Proteos Biopolis Drive 61号，新加坡138673。
    2个
    新加坡国立新加坡大学新加坡大学林永林医学院消化系和肝病科。
    3
    新加坡免疫学网络，A * STAR RE，新加坡，新加坡。
    4
    IMCB，Tessa Therapeutics Pvt Ltd，新加坡，新加坡。
    5
    新加坡科学技术研究局分子与细胞生物学研究所（IMCB）的转化免疫学计划（A * STAR）研究实体（RE），新加坡Proteos Biopolis Drive 61号，新加坡138673。 [email protected]。
    6
    新加坡新加坡国立大学Yong Loo Lin医学院微生物学和免疫学系，新加坡，新加坡。 [email protected]。
    7
    美国德克萨斯州韦科，贝勒大学生物医学研究所。 [email protected]。

    PMID：33811250 DOI：10.1038 / s41598-021-86836-5

抽象的

我们的目标是检查慢性乙型肝炎（CHB）患者的细胞因子/趋化因子反应差异，以了解抗病毒治疗期间HBsAg丢失（功能性治愈）的免疫机制。我们采用了无偏见的机器学习策略来阐明在随机临床中通过peg-干扰素-α（peg-IFN-α）附加或转换治疗实现HBsAg丧失的CHB核苷（t）侧类似物治疗患者的免疫途径审判。在基线，HBsAg缺失前后，HBsAg缺失前后，比较血浆中的细胞因子/趋化因子。在HBsAg丧失之前，Peg-IFN-α治疗导致更高水平的IL-27，IL-12p70，IL-18，IL-13，IL-4，IL-22和GM-CSF。对细胞因子，趋化因子和可溶性因子的概率网络分析表明，动态树突细胞驱动的NK和T细胞免疫应答与HBsAg丢失有关。贝叶斯网络分析显示，由MIG和I-TAC中央模块控制的主要的髓样驱动的1型炎症反应，导致附加臂中的HBsAg丢失。在转换臂中，HBsAg丢失与T细胞活化模块有关，高水平的CD40L提示T细胞活化。我们的研究结果表明，peg-IFN-α治疗发现了一种以上的HBsAg丢失免疫途径。一种是由髓样驱动的1型反应，另一种是T细胞活化。

StephenW

https://www.nature.com/articles/s41598-021-86836-5.pdf