肝組織學組織中CD8 + PD-1 + T細胞的減少與慢性乙型肝炎患者的

StephenW

The reduction in CD8 + PD-1 + T cells in liver histological tissue is related to Pegylated IFN-α therapy outcomes in chronic hepatitis B patients
Ruyu Liu  1 , Yanhui Chen  2   3 , Jiang Guo  4 , Minghui Li  5 , Yao Lu  5 , Lu Zhang  5 , Ge Shen  5 , Shuling Wu  5 , Min Chang  5 , Leiping Hu  5 , Hongxiao Hao  5 , Henghui Zhang  6   7 , Yao Xie  8
Affiliations
Affiliations

    1
    Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing, 100015, China. [email protected].
    2
    Institute of Infectious Diseases, Beijing Ditan Hospital, Beijing Key Laboratory of Emerging Infectious Diseases, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing, 100015, China.
    3
    Genecast Precision Medicine Technology Institute, 35 North Garden Rd., Haidian District, Beijing, 100089, China.
    4
    Tumor Interventional Department, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing, 100015, China.
    5
    Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing, 100015, China.
    6
    Institute of Infectious Diseases, Beijing Ditan Hospital, Beijing Key Laboratory of Emerging Infectious Diseases, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing, 100015, China. [email protected].
    7
    Genecast Precision Medicine Technology Institute, 35 North Garden Rd., Haidian District, Beijing, 100089, China. [email protected].
    8
    Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University, No. 8 Jingshun East Street, Chaoyang District, Beijing, 100015, China. [email protected].

    PMID: 32778058 DOI: 10.1186/s12879-020-05320-z

Abstract

Background: Antiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy.

Methods: Thirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+ T cells, CD4+ T cells, CD68+ mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence.

Results: The overall median frequency of CD8+ T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p < 0.01). In the FIER (fibrosis and inflammation response with HBeAg seroconversion) group, CD8+PD-1+ T cells significantly decreased at 6 months (p < 0.05), while CD8+PD-1- T cells had no significant difference. On the contrary, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8+PD-1- T cells significantly decreased after 6 months of PEG-IFN-α treatment (p < 0.05), while CD8+PD-1+ T cells had no significant difference. In addition, the levels of CD68+ mononuclear cells in the FIER group showed an overall increasing trend after treatment (p < 0.05).

Conclusions: The changes in the levels of CD8+PD-1+ T cells and CD68+ mononuclear cells may be related to the response to PEG-IFN-α therapy.

Keywords: CD4+ T cells; CD68+ mononuclear cells; CD8+ T cells; Chronic hepatitis B; PD-1; Pegylated IFN-α.
Grant support

    2018ZX10302207/National Key Sci-Tech Special Project of China
    PX2018060/Beijing Hospitals Authority Incubating Program
    QML20181803/Beijing Hospitals Authority Youth Programme

StephenW

肝組織學組織中CD8 + PD-1 + T細胞的減少與慢性乙型肝炎患者的聚乙二醇化IFN-α治療結果有關
劉如玉1，陳彥輝2 3，姜國4，李明輝5，姚璐5，盧章5，葛申5，吳淑玲5，民昌5，胡雷平5，洪曉浩5，張恆輝6 7，妖X8
隸屬關係
隸屬關係

    1個
    首都醫科大學附屬北京地壇醫院肝病科2，北京市朝陽區經順東街8號，北京100015。 [email protected]。
    2
    首都醫科大學附屬北京地壇醫院傳染病研究所，北京市新興傳染病重點實驗室，北京市朝陽區京順東大街8號，北京100015
    3
    北京市海淀區花園北路35號基因鑄造精密醫學技術研究所，北京100089。
    4
    首都醫科大學附屬北京地壇醫院腫瘤介入科，北京市朝陽區京順東大街8號，北京100015
    5
    首都醫科大學附屬北京地壇醫院肝病科2，北京市朝陽區京順東街8號，北京100015。
    6
    首都醫科大學附屬北京地壇醫院傳染病研究所，北京市新興傳染病重點實驗室，北京市朝陽區京順東大街8號，北京100015 [email protected]。
    7
    北京市海淀區花園北路35號基因鑄造精密醫學技術研究所，北京100089。 [email protected]。
    8
    首都醫科大學附屬北京地壇醫院肝病科2，北京市朝陽區經順東街8號，北京100015。 [email protected]。

    PMID：32778058 DOI：10.1186 / s12879-020-05320-z

抽象

背景：對於患有免疫活性的慢性乙型肝炎（CHB）的患者，建議使用抗病毒治療，以減少發生肝臟相關並發症的風險。但是，聚乙二醇化干擾素-α（PEG-IFN-α）治療的結果在CHB患者之間有所不同。我們旨在確定可影響接受抗病毒PEG-IFN-α單藥治療的CHB患者預後的因素。

方法：本研究納入了接受PEG-IFN-α單藥治療的32例CHB患者。所有患者均在基線和治療開始後6個月進行了兩次肝活檢。通過免疫熒光檢查64個肝活檢標本中的CD8 + T細胞，CD4 + T細胞，CD68 +單核細胞和PD-1水平。

結果：32例CHB患者肝組織中CD8 + T細胞的總體中位數頻率在開始治療後6個月顯著降低（p <0.01）。在FIER（HBeAg血清轉化引起的纖維化和炎症反應）組中，CD8 + PD-1 + T細胞在6個月時顯著減少（p <0.05），而CD8 + PD-1-T細胞沒有顯著差異。相反，在FIENR（無纖維化和炎症反應以及HBeAg血清轉化）組中，經過PEG-IFN-α治療6個月後，CD8 + PD-1-T細胞顯著減少（p <0.05），而CD8 + PD- 1+ T細胞無明顯差異。此外，FIER組的CD68 +單核細胞水平在治療後總體呈上升趨勢（p <0.05）。

結論：CD8 + PD-1 + T細胞和CD68 +單核細胞水平的變化可能與對PEG-IFN-α治療的反應有關。

關鍵詞：CD4 + T細胞CD68 +單核細胞； CD8 + T細胞；慢性乙型肝炎； PD-1；聚乙二醇化的IFN-α。
贈款支持

    2018ZX10302207 /國家重點科技專項
    PX2018060 /北京醫院管理局孵化計劃
    QML20181803 /北京市醫院管理局青年計劃

StephenW

https://bmcinfectdis.biomedcentr ... /s12879-020-05320-z