中文English
ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 38 Issue 7
Jul.  2022
Turn off MathJax
Article Contents

Changes and clinical significance of natural killer-like B cells, natural killer cells, and B cells in peripheral blood of patients with hepatitis B virus infection

DOI: 10.3969/j.issn.1001-5256.2022.07.008
Research funding:

National Natural Science Foundation of China (31370856);

National Natural Science Foundation of China (81671555)

More Information
  • Corresponding author: ZHANG Ye, zhangyefmmu@hotmail.com(ORCID: 0000-0002-2573-5471)
  • Received Date: 2021-11-24
  • Accepted Date: 2022-02-09
  • Published Date: 2022-07-20
  •   Objective  To investigate the changes of natural killer-like B (NKB) cells, natural killer (NK) cells, and B cells and their correlation with clinical indices in patients with hepatitis B virus (HBV) infection.  Methods  A total of 15 patients with acute hepatitis B (AHB), 30 patients with chronic hepatitis B (CHB), 29 asymptomatic HBV carriers (ASCs), and 12 controls who attended Tangdu Hospital from January 2017 and December 2018 were enrolled. Peripheral blood samples were collected, and plasma and peripheral blood mononuclear cells (PBMCs) were isolated. ELISA was used to measure the plasma levels of interleukin-18 (IL-18) and interferon-γ (IFNγ), and enzyme-linked immunospot assay was used to measure the level of IFNγ secreted by HBV-specific CD8+ T cells; flow cytometry was used to measure the percentages of CD3-CD19+CD56+CD16+ NKB cells, different NK cell subsets (including CD3-CD19-CD56highCD16- NK cells, CD3-CD19-CD56+CD16+ NK cells, and CD3-CD19-CD56-CD16+ NK cells), and their correlation with viral replication and liver inflammation markers was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups; non-normally distributed continuous data were expressed as M(P25-P75), and the Kruskal-Wallis H test was used for comparison between multiple groups; the Pearson correlation test was used for correlation analysis.  Results  There was a significant difference in the percentage of CD3-CD19+CD16+CD56+ NKB cells between the AHB patients, CHB patients, ASCs, and controls (F = 16.42, P < 0.000 1), and the CHB patients had a significantly lower percentage of NKB cells than the AHB patients, ASCs, and controls (0.79%±0.13% vs 0.94%±0.15%/1.02%±0.12%/1.11%±0.27%, all P < 0.001). There was a significant difference in plasma IL-18 level between the AHB patients, CHB patients, ASCs, and controls (F = 5.733, P = 0.001); the CHB patients had a significantly lower IL-18 level than the AHB patients and the controls (259.30±70.09 pg/mL vs 336.00±103.00 pg/mL and 319.30±64.80 pg/mL, both P < 0.05), and ASCs had a significantly lower IL-18 level (258.60±59.82 pg/mL) than the AHB patients and the controls (both P < 0.01), while there was no significant difference in plasma IL-18 level between the CHB patients and ASCs (P = 0.965). There were no significant differences in the percentage of CD3-CD19-CD56highCD16- NK cells, CD3-CD19-CD56+CD16+ NK cells, CD3-CD19-CD56-CD16+ NK cells, and B cells between the four groups (all P > 0.05). The CHB patients had a significantly lower plasma IFNγ level than the AHB patients, ASCs, and controls (all P < 0.01). The percentage of NKB cells and the level of IL-18 were not significantly correlated with HBV DNA quantification or alanine aminotransferase level (all P > 0.05). In the CHB patients, the percentage of NKB cells was positively correlated with plasma IL-18 level (r = 0.432, P = 0.017) and the level of IFNγ secreted by HBV-specific CD8+ T cells (r =0.493, P=0.006).  Conclusion  NKB cells and IL-18 might be involved in the chronicity of HBV infection and is associated with the natural history of chronic HBV infection.

     

  • loading
  • [1]
    LIN CL, KAO JH. Natural history of acute and chronic hepatitis B: The role of HBV genotypes and mutants[J]. Best Pract Res Clin Gastroenterol, 2017, 31(3): 249-255. DOI: 10.1016/j.bpg.2017.04.010.
    [2]
    WU J, HAN M, LI J, et al. Immunopathogenesis of HBV infection[J]. Adv Exp Med Biol, 2020, 1179: 71-107. DOI: 10.1007/978-981-13-9151-4_4.
    [3]
    WANG S, XIA P, CHEN Y, et al. Natural killer-like B cells prime innate lymphocytes against microbial infection[J]. Immunity, 2016, 45(1): 131-144. DOI: 10.1016/j.immuni.2016.06.019.
    [4]
    Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association. The guideline of prevention and treatment for chronic hepatitis B: a 2015 update[J]. J Clin Hepatol, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.

    中华医学会肝病学分会, 中华医学会感染病学分会. 慢性乙型肝炎防治指南(2015年更新版)[J]. 临床肝胆病杂志, 2015, 31(12): 1941-1960. DOI: 10.3969/j.issn.1001-5256.2015.12.002.
    [5]
    DONG J, YANG XF, WANG LX, et al. Modulation of tim-3 expression by antigen-dependent and -independent factors on T cells from patients with chronic hepatitis B virus infection [J]. Front Cell Infect Microbiol, 2017, 7: 98. DOI: 10.3389/fcimb.2017.00098.
    [6]
    LI L, TANG YX, HE W, et al. Estimated sample content of commonly used clinical trial designs [J]. Systems Med, 2018, 3(9): 191-193. DOI: 10.19368/j.cnki.2096-1782.2018.09.191.

    李黎, 唐雨欣, 何伟, 等. 常用临床试验设计的样本含量估计[J]. 系统医学, 2018, 3(9): 191-193. DOI: 10.19368/j.cnki.2096-1782.2018.09.191.
    [7]
    MANICKAM C, NWANZE C, RAM DR, et al. Progressive lentivirus infection induces natural killer cell receptor-expressing B cells in the gastrointestinal tract[J]. AIDS, 2018, 32(12): 1571-1578. DOI: 10.1097/QAD.0000000000001855.
    [8]
    ZHANG Y, KUANG W, LI D, et al. Natural killer-like B cells secreting interleukin-18 induces a proinflammatory response in periodontitis[J]. Front Immunol, 2021, 12: 641562. DOI: 10.3389/fimmu.2021.641562.
    [9]
    KERDILES YM, ALMEIDA FF, THOMPSON T, et al. Natural-killer-like B cells display the phenotypic and functional characteristics of conventional B cells[J]. Immunity, 2017, 47(2): 199-200. DOI: 10.1016/j.immuni.2017.07.026.
    [10]
    RASCLE P, JACQUELIN B, PETITDEMANGE C, et al. NK-B cell cross talk induces CXCR5 expression on natural killer cells[J]. iScience, 2021, 24(10): 103109. DOI: 10.1016/j.isci.2021.103109.
    [11]
    LIU S, YANG L, JIA S, et al. Interleukin-35 suppresses the activity of natural killer-like B cells in patients with hepatocellular carcinoma[J]. Int Immunopharmacol, 2021, 100: 108161. DOI: 10.1016/j.intimp.2021.108161.
    [12]
    LU Y, BAO JG, DENG Y, et al. Role of IL-18 gene promoter polymorphisms, serum IL-18 levels, and risk of hepatitis B virus-related liver disease in the Guangxi Zhuang Population: a retrospective case-control study[J]. Asian Pac J Cancer Prev, 2015, 16(14): 6019-6026. DOI: 10.7314/apjcp.2015.16.14.6019.
    [13]
    CHEN YX, HUANG R, WU C. Influence of pregnancy on the natural history of chronic hepatitis B virus infection[J]. J Clin Hepatol, 2019, 35(7): 1430-1434. DOI: 10.3969/j.issn.1001-5256.2019.07.004.

    陈雨欣, 黄睿, 吴超. 妊娠对慢性HBV感染自然史的影响[J]. 临床肝胆病杂志, 2019, 35(7): 1430-1434. DOI: 10.3969/j.issn.1001-5256.2019.07.004.
    [14]
    LIN CL, KAO JH. Natural history of acute and chronic hepatitis B: The role of HBV genotypes and mutants [J]. Best Pract Res Clin Gastroenterol, 2017, 31(3): 249-255. DOI: 10.1016/j.bpg.2017.04.010.
    [15]
    LIU S, YANG L, JIA S, et al. Interleukin-35 suppresses the activity of natural killer-like B cells in patients with hepatocellular carcinoma[J]. Int Immunopharmacol, 2021, 100: 108161. DOI: 10.1016/j.intimp.2021.108161.
    [16]
    PENG MJ, YANG XF, WEI X, et al. Influence of hepatitis B virus infection on intrahepatic natural killer cells and innate lymphoid cell 22[J]. J Clin Hepatol, 2016, 32(10): 1883-1887. DOI: 10.3969/j.issn.1001-5256.2016.10.012.

    彭梅娟, 杨晓飞, 魏欣, 等. HBV感染对肝脏自然杀伤细胞和固有淋巴样细胞22的影响[J]. 临床肝胆病杂志, 2016, 32(10): 1883-1887. DOI: 10.3969/j.issn.1001-5256.2016.10.012.
    [17]
    LIANG HJ, CUI YH, WANG YP, et al. Matrix metallopeoteinase regulates natural killer cells function in methicili-resistant staphylococcus aureus sepsis [J]. Chin J Emerg Med, 2020, 29(6): 835-840. DOI: 10.3760/cma.j.issn.1671-0282.2020.06.019.

    梁海军, 崔艳慧, 王燕平, 等. 基质金属蛋白酶对MRSA脓毒症患者NK细胞的调控作用[J]. 中华急诊医学杂志, 2020, 29(6): 835-840. DOI: 10.3760/cma.j.issn.1671-0282.2020.06.019.
    [18]
    QU XJ, LI MH, CAO WH, et al. Study the change of NK cells in HBV infection [J]. Chin J Exp Clin Virol, 2016, 30(5): 439-443. DOI: 10.3760/cma.j.issn.1003-9279.2016.05.006.

    屈晓晶, 李明慧, 曹卫华, 等. NK细胞在HBV感染中的作用研究[J]. 中华实验和临床病毒学杂志, 2016, 30(5): 439-443. DOI: 10.3760/cma.j.issn.1003-9279.2016.05.006.
    [19]
    CAI HN, XU Y, CHEN XY, et al. Effect of HBV infection on biological activity of NK cells cultured in vitro[J/CD]. Chin J Hepat Surg(Electronic Edition), 2020, 9(3): 274-277. DOI: 10.3877/cma.j.issn.2095-3232.2020.03.016.

    蔡惠宁, 许燕, 陈晓燕, 等. HBV感染对体外培养NK细胞生物活性影响的研究[J/CD]. 中华肝脏外科手术学电子杂志, 2020, 9(3): 274-277. DOI: 10.3877/cma.j.issn.2095-3232.2020.03.016.
    [20]
    LIAN JQ, YANG XF, ZHAO RR, et al. Expression profiles of circulating cytokines, chemokines and immune cells in patients with hepatitis B virus infection[J]. Hepat Mon, 2014, 14(6): e18892. DOI: 10.5812/hepatmon.18892.
    [21]
    JIANG Y, CHEN Y, CHEN L, et al. Impaired circulating CD56dim NK cells are associated with decompensation of HBV-related cirrhosis[J]. Hum Immunol, 2020, 81(1): 32-40. DOI: 10.1016/j.humimm.2019.11.006.
    [22]
    CHEN Y, TIAN Z. HBV-Induced Immune Imbalance in the Development of HCC[J]. Front Immunol, 2019, 10: 2048. DOI: 10.3389/fimmu.2019.02048.
    [23]
    CAI Y, YIN W. The multiple functions of B cells in chronic HBV infection[J]. Front Immunol, 2020, 11: 582292. DOI: 10.3389/fimmu.2020.582292.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(3)  / Tables(1)

    Article Metrics

    Article views (475) PDF downloads(55) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return