Segbefia Selorm P, Asandem Diana A, Pobee Abigail, Asare Bright, Prah Ahu Diana, Baba-Adam Rawdat, Amponsah Jones Amo, Kyei-Baafour Eric, van der Puije William, Osei Frank, Teye-Adjei Doreen, Agyemang Seth, Brenko Theophilus, Bentum-Ennin Lutterodt, Tetteh John K A, Bonney Kofi J H, Sakyi Samuel Asamoah, Amoah Linda E, Kusi Kwadwo A
Department of Immunology, NMIMR, College of Health Sciences University of Ghana Accra Ghana.
Department of Molecular Medicine, School of Medicine and Dentistry College of Health Sciences, KNUST Kumasi Ghana.
Health Sci Rep. 2024 Jul 29;7(8):e2280. doi: 10.1002/hsr2.2280. eCollection 2024 Aug.
Chronic hepatitis B virus (CHB) infection remains a major public health problem. The American Association for the Study of Liver Diseases (AASLD) 2018 Hepatitis B Guidelines provide that CHB individuals not requiring antiviral therapy yet are monitored to determine the need for antiviral therapy in the future; however, these tests do not include measurement of cytokines and immune cell characterization. This case-control study compared the cytokine and immune checkpoint protein expression profiles between CHB individuals not yet on antiviral treatment and hepatitis B virus (HBV)-negative individuals.
CD4 and CD8 T cells from CHB and HBV-negative individuals were characterized for immune checkpoint proteins programmed cell death-1 (PD1), T cell Immunoglobulin domain and mucin domain-containing protein 3 (TIM-3), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) (CD152), and a memory marker CXCR3 (CD183) using flow cytometry. Malaria-induced cytokine expression levels were determined by stimulating their blood cells with 3D7 strain antigens (CSP, AMA-1, and TRAP) in whole blood assays, and cytokine levels were measured using a 13-plex Luminex kit.
HBV-negative and CHB individuals had comparable levels of CD4+ and CD8+ T cells. However, a proportion of the CD4+ and CD8+ populations from both groups, which were CXCR3+, expressed PD-1 and CD152. The ability to produce cytokines in response to malaria antigen stimulation was not significantly different between the groups.
These findings support excluding CHB individuals from antiviral therapy at this stage of infection. However, CHB individuals require regular monitoring to determine the need for later antiviral treatment.
慢性乙型肝炎病毒（CHB）感染仍是一个主要的公共卫生问题。美国肝病研究协会（AASLD）2018年《乙型肝炎指南》规定，对于尚未需要抗病毒治疗的CHB患者需进行监测，以确定未来是否需要抗病毒治疗；然而，这些检测不包括细胞因子的测量和免疫细胞特征分析。本病例对照研究比较了尚未接受抗病毒治疗的CHB患者与乙型肝炎病毒（HBV）阴性个体之间的细胞因子和免疫检查点蛋白表达谱。
使用流式细胞术对CHB患者和HBV阴性个体的CD4和CD8 T细胞进行免疫检查点蛋白程序性细胞死亡蛋白1（PD1）、含T细胞免疫球蛋白结构域和粘蛋白结构域蛋白3（TIM-3）以及细胞毒性T淋巴细胞相关抗原4（CTLA-4）（CD152）和记忆标志物CXCR3（CD183）的特征分析。通过在全血检测中用3D7株抗原（CSP、AMA-1和TRAP）刺激其血细胞来测定疟疾诱导的细胞因子表达水平，并使用13种细胞因子的Luminex试剂盒测量细胞因子水平。
HBV阴性和CHB患者的CD4+和CD8+ T细胞水平相当。然而，两组中CXCR3+的CD4+和CD8+细胞群体中有一部分表达PD-1和CD152。两组之间对疟疾抗原刺激产生细胞因子的能力没有显著差异。
这些发现支持在感染的这个阶段将CHB患者排除在抗病毒治疗之外。然而，CHB患者需要定期监测以确定后期抗病毒治疗的必要性。
