Dynamic changes of the proportion of HLA-DR and CD38 coexpression subsets on T lymphocytes during IFN-based chronic hepatitis B treatment

Yanjie Lin; Ge Shen; Si Xie; Xiaoyue Bi; Huihui Lu; Liu Yang; Tingting Jiang; Wen Deng; Shiyu Wang; Lu Zhang; Yao Lu; Yuanjiao Gao; Hongxiao Hao; Shuling Wu; Ruyu Liu; Min Chang; Mengjiao Xu; Leiping Hu; Xiaoxue Chen; Ronghai Huang; Minghui Li; Yao Xie

doi:10.3389/fimmu.2022.1116160

Dynamic changes of the proportion of HLA-DR and CD38 coexpression subsets on T lymphocytes during IFN-based chronic hepatitis B treatment

Front Immunol. 2023 Jan 24:13:1116160. doi: 10.3389/fimmu.2022.1116160. eCollection 2022.

Authors

Yanjie Lin¹, Ge Shen², Si Xie³, Xiaoyue Bi², Huihui Lu⁴, Liu Yang², Tingting Jiang², Wen Deng², Shiyu Wang², Lu Zhang², Yao Lu², Yuanjiao Gao², Hongxiao Hao², Shuling Wu², Ruyu Liu², Min Chang², Mengjiao Xu², Leiping Hu², Xiaoxue Chen², Ronghai Huang⁵, Minghui Li^{1

2}, Yao Xie^{1

2}

Affiliations

¹ Department of Hepatology Division 2, Peking University Ditan Teaching Hospital, Beijing, China.
² Department of Hepatology Division 2, Beijing Ditan 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 Obstetrics and Gynecology, Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ Department of General Surgery, Beijing Ditan Hospital, Capital Medical University, Beijing, China.

Abstract

Background: To investigate the changes of human leukocyte antigen DR (HLA-DR) and CD38 coexpression subsets on T lymphocytes following interferon (IFN) therapy for those who have chronic hepatitis B (CHB).

Methods: A prospective cohort of CHB patients participated in this study. CHB patients without IFN treatment (including naïve and nucleoside [nucleotide] analogs [NAs]-treated patients) were given pegylated interferon alfa (Peg-IFNα) treatment. Peripheral blood samples were taken at baseline, 4 weeks and 12-24 weeks of Peg-IFNα treatment. For the patients who entered the Peg-IFNα plateau phase due to the stagnation of the decrease in HBsAg, and Peg-IFNα was discontinued and Peg-IFNα therapy was resumed after an interval of 12-24 weeks. During the interval, they received first-line NAs treatment. Peripheral blood samples were collected at the baseline of the plateau phase, 12-24 weeks of intermittent treatment, and 12-24 weeks of Peg-IFNα retreatment. The peripheral blood samples were taken to determine virological, serological and biochemical indices of hepatitis B virus (HBV), and T lymphocyte related phenotypes were detected using flow cytometry.

Results: In the process of long-term treatment of Peg-IFNα, the percentage of HLA-DR⁺CD38^dim subsets increased significantly at first, then decreased gradually, while the percentage of HLA-DR⁺CD38^hi subsets markedly increased. During long-term Peg-IFNα treatment, there was a considerable negative correlation between HBsAg and the HLA-DR⁺CD38^hi subset percentage. The persistent high proportion of HLA-DR⁺CD38^hi subsets was related to the occurrence of Peg-IFNα plateau phase. After Peg-IFNα intermittent treatment, the percentage of HLA-DR⁺CD38^hi subsets decreased significantly. After Peg-IFNα retreatment, the level of HBsAg began to decrease again. At the same time, the percentage of HLA-DR⁺CD38^hi subsets significantly increased, but it was still lower than that at the baseline level.

Conclusions: The spectrum of HLA-DR and CD38 coexpression subsets on T lymphocytes changed during the long-term treatment of IFN. The establishment of the IFN plateau phase was linked to the persistence of a considerable proportion of HLA-DR⁺CD38^hi subsets on T lymphocytes. IFN intermittent treatment could significantly reduce the proportion of HLA-DR⁺CD38^hi subsets, helping regain the antiviral efficacy of IFN during IFN retreatment.

Keywords: CD38; HLA-DR; chronic hepatitis B; interferon; intermittent therapy; plateau phase.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

HLA-DR Antigens
Hepatitis B Surface Antigens*
Hepatitis B, Chronic*
Humans
Interferon-alpha / therapeutic use
Prospective Studies
T-Lymphocytes

Substances

Hepatitis B Surface Antigens
HLA-DR Antigens
Interferon-alpha
CD38 protein, human

Grants and funding

The Digestive Medical Coordinated Development Center of Beijing Hospitals Authority (XXZ0302 and XXT28). Project Supported by Beijing Science and Technology Commission (Z211100002921059). High-level Public Health Technical Personnel Training Program of Beijing Municipal Health Commission (2022-3-050). National Science and Technology Major Project of China (2017ZX10201201-001-006, 2017ZX10201201-002-006, 2018ZX10715-005-003-005). The Capital Health Research and Development of Special (2022-1-2172). Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support (XMLX 202127). National Key R&D Program of China (2022YFC2603505).