浆细胞样树突状细胞上功能分子的表达与 PEG-IFN α-2a 治疗期

StephenW

浆细胞样树突状细胞上功能分子的表达与 PEG-IFN α-2a 治疗期间 HBeAg 阳性患者的 HBsAg 丢失有关
曹卫华 1 2 , 思燮 3 , 张璐 1 , 小月碧 1 , 林燕杰 4 , 刘洋 1 , 姚璐 1 , 刘如玉 1 , 闵昌 1 , 吴淑玲 1 , 葛深 1 , 董建平 5 , 姚谢 1 4 , 李明辉 1 4
隶属关系
隶属关系

    1
    【作者单位】： 首都医科大学北京地坛医院肝病二科;
    2
    【作者单位】： 首都医科大学密云教学医院感染科;
    3
    清华大学临床医学院北京清华长庚医院肝胆胰中心肝病科
    4
    【作者单位】： 北京大学地坛教学医院肝病二科;
    5
    【作者单位】： 北京大学第三医院北京海淀区海淀医院感染科;

    PMID：35663955 PMCID：PMC9160736 DOI：10.3389/fimmu.2022.891424

抽象的

目的：慢性乙型肝炎（CHB）患者抗病毒治疗的理想终点是清除乙型肝炎表面抗原（HBsAg）。本研究旨在评估浆细胞样树突状细胞 (pDC) 上功能分子的表达是否与聚乙二醇干扰素 α-2a (PEG IFN α-2a) 治疗期间 HBeAg 阳性患者的 HBsAg 丢失相关。

方法：对接受 PEG-IFN α-2a 治疗并随访 4 年的 HBeAg 阳性 CHB 患者进行单中心前瞻性队列研究。通过 PEG-IFN α-2a 治疗实现的 HBsAg 清除、HBeAg 消失和无法检测到的 HBV DNA 被认为是功能性治愈。在开始治疗时、治疗 12 周和 24 周后，测量外周血中 pDC 和 CD86+ pDC 的频率，以及 pDC 表面 CD86 (CD86MFI) 的平均荧光强度。

结果：入组的 63 名患者中，17 名患者 HBsAg 消失。非功能性治愈组的基线HBV DNA载量显着高于功能性治愈组，未功能性治愈的患者CD86+ pDC%显着降低。 HBV DNA 载量 (OR=0.146, P = 0.002) 和 CD86+ pDC% (OR=1.183, P = 0.025) 是二元逻辑回归分析证实的与功能治愈相关的独立因素。在功能性治愈组中，与基线相比，治疗 12 周和 24 周后 HBsAg、HBeAg 和 HBV DNA 载量显着下降。在非功能性治愈组，治疗 12 周后，CD86+ pDC% 和 CD86MFI 从基线显着增加。在功能性治愈组中，与基线相比，pDC% 在 24 周时显着增加，而 CD86MFI 在治疗 24 周后显着增加。

结论：基线HBV DNA载量越低，基线CD86+ pDC%越高，患者越容易获得功能性治愈。

关键词：慢性乙型肝炎；功能性治愈；乙型肝炎表面抗原；干扰素；浆细胞样树突状细胞。

版权所有 © 2022 曹、谢、张、毕、林、杨、卢、刘、常、吴、沉、董、谢、李。
利益冲突声明

作者声明，该研究是在没有任何可能被解释为潜在利益冲突的商业或财务关系的情况下进行的。审稿人 LJ 在审稿时向负责编辑声明了与作者 WC、LZ、XB、YL、LY、YJL、RL、MC、SW、GS、YX 和 ML 的共同父母关系。

StephenW

Expression of Functional Molecule on Plasmacytoid Dendritic Cells Is Associated With HBsAg Loss in HBeAg-Positive Patients During PEG-IFN α-2a Treatment
Weihua Cao  1   2 , Si Xie  3 , Lu Zhang  1 , Xiaoyue Bi  1 , Yanjie Lin  4 , Liu Yang  1 , Yao Lu  1 , Ruyu Liu  1 , Min Chang  1 , Shuling Wu  1 , Ge Shen  1 , Jianping Dong  5 , Yao Xie  1   4 , Minghui Li  1   4
Affiliations
Affiliations

    1
    Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, Beijing, China.
    2
    Department of Infectious Diseases, Miyun Teaching Hospital, Capital Medical University, Beijing, China.
    3
    Division of Hepatology, Hepato-Pancreato-Biliary Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China.
    4
    Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China.
    5
    Department of Infectious Diseases, Haidian Hospital, Beijing Haidian Section of Peking University Third Hospital, Beijing, China.

    PMID: 35663955 PMCID: PMC9160736 DOI: 10.3389/fimmu.2022.891424

Abstract

Objective: The ideal endpoint of antiviral therapy in chronic hepatitis B (CHB) patients is to clear hepatitis B surface antigen (HBsAg). This study aimed to evaluate whether the expression of functional molecules on plasmacytoid dendritic cells (pDCs) is associated with HBsAg loss in HBeAg-positive patients during peginterferon alpha-2a (PEG IFN α-2a) therapy.

Methods: A single-center prospective cohort study was performed in HBeAg-positive CHB patients who were treated with PEG-IFN α-2a and followed up for 4 years. HBsAg clearance, HBeAg loss and undetectable HBV DNA achieved by PEG-IFN α-2a therapy was considered as functional cure. The frequencies of pDC and CD86+ pDC in peripheral blood, and the mean fluorescence intensity of CD86 (CD86MFI) on the surface of pDC were measured at starting therapy, after 12 and 24 weeks of therapy.

Results: Of 63 patients enrolled, 17 patients achieved HBsAg loss. The baseline HBV DNA load in Non-functional-cure group was significantly higher than that in Functional cure group, and the CD86+ pDC% was significantly lower in patients without functional cure. HBV DNA load (OR=0.146, P = 0.002) and CD86+ pDC% (OR=1.183, P = 0.025) were independent factors associated with functional cure confirmed by binary logistic regression analysis. In the Functional cure group, HBsAg, HBeAg, and HBV DNA loads decreased remarkably after 12 weeks and 24 weeks of treatment compared to baseline. In Non-functional-cure group, CD86+ pDC% and CD86MFI increased significantly from baseline after 12 weeks of treatment. In the Functional cure group, compared with baseline, pDC% increased significantly at 24 weeks, while CD86MFI increased significantly after 24 weeks of treatment.

Conclusion: The lower the baseline HBV DNA load and the more the baseline CD86+ pDC%, the easier it is for patients to obtain functional cure.

Keywords: chronic hepatitis B; functional cure; hepatitis B surface antigen; interferon; plasmacytoid dendritic cells.

Copyright © 2022 Cao, Xie, Zhang, Bi, Lin, Yang, Lu, Liu, Chang, Wu, Shen, Dong, Xie and Li.
Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The Reviewer LJ declared a shared parent affiliation with the authors WC, LZ, XB, YL, LY, YJL, RL, MC, SW, GS, YX, and ML to the handling editor at the time of review.

StephenW

https://www.frontiersin.org/arti ... mmu.2022.891424/pdf