1型自身免疫性肝炎患者外周血T淋巴细胞PD-L1的表达情况及其与肝脏炎症活动度的相关性分析

熊克宫; 柯坤宇; 孔金峰; 柳丽娟; 陈丽芳; 林小钦

doi:10.3969/j.issn.1001-5256.2018.06.023

1型自身免疫性肝炎患者外周血T淋巴细胞PD-L1的表达情况及其与肝脏炎症活动度的相关性分析

DOI: 10.3969/j.issn.1001-5256.2018.06.023

福建医科大学孟超肝胆医院福建医科大学附属传染病医院肝病内科

基金项目:

福州市卫生计生科技计划项目(2016-S-wq7)；福州市科技强院建设项目(2017-S-131-1)；福建省科技计划项目(2018D0006)；

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中图分类号: R575.1
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出版历程
- 收稿日期: 2017-12-11
- 出版日期: 2018-06-20

Expression of programmed death-ligand 1 on peripheral blood T cells and its correlation with liver inflammation grade in patients with type 1 autoimmune hepatitis

Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University & Affiliated Infectious Diseases Hospital of Fujian Medical University

Research funding:

摘要

摘要:
目的研究1型自身免疫性肝炎（AIH）患者外周血CD4+、CD8+T淋巴细胞表面程序性细胞死亡因子配体1（PD-L1）的表达情况,并探讨其与肝脏炎症活动度的相关性。方法以2014年1月-2017年8月福建医科大学孟超肝胆医院收治的62例1型AIH患者（活动期43例和缓解期19例）为研究对象,并选择20例健康者为对照组。采用流式细胞术检测外周血CD4+、CD8+T淋巴细胞表面PD-L1的表达率。计量资料两组组间比较采用t检验或Mann-Whitney U检验,多组比较采用单因素方差分析及LSD-t或Kruskal-Wallis H检验,计数资料组间比较采用χ2检验,相关性分析采用Pearson和Spearman秩相关分析。结果 1型AIH组患者外周血CD4+、CD8+T淋巴细胞表面PD-L1的表达率[（10.94±4.52）%、（9.93±3.32）%]均高于对照组[（5.42±2.64）%、（4.86±2.16）%]（t值分别为7.12、6.41,P值均<0.05）;1型AIH活动期患者外周血CD4+、CD8+T淋巴细胞表面PD-L1的表达率[（12.45±5.61）%、（11.1...
- 自身免疫性肝炎 /
- T淋巴细胞 /
- 程序性细胞死亡因子配体1
Abstract:
Objective To investigate the expression of programmed death-ligand 1 (PD-L1) on the surface of peripheral blood CD4+and CD8+T cells and its correlation with liver inflammation grade in patients with type 1 autoimmune hepatitis (AIH) . Methods A total of 62 patients with type 1 AIH (43 in the active stage and 19 in the remission stage) who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from January 2014 to August 2017 were enrolled, and 20 healthy persons were enrolled as control group. Flow cytometry was used to measure the expression of PD-L1 on the surface of eripheral blood CD4+and CD8+T cells. The t-test or the Mann-Whitney U test was used for the comparison of continuous data between two groups, and a one-way analysis of variance and the least significant difference t-test or the Kruskal-Wallis H test were used for the comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups; Pearson correlation and Spearman rank analysis was performed to investigate correlation.Results Compared with the control group, the type 1 AIH group had significantly higher expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells (10. 94% ± 4. 52%/9. 93% ± 3. 32% vs 5. 42% ± 2. 64%/4. 86% ± 2. 16%, t = 7. 12 and 6. 41, both P < 0. 05) ; compared with the remission stage group and the control group, the active stage group had significantly higher expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells (12. 45% ± 5. 61%/11. 13% ± 4. 63% vs 7. 88% ± 3. 85%/7.36% ± 3. 12% and 5. 42% ± 2. 64%/4. 86% ± 2. 16%, F = 15. 76 and 13. 54, both P < 0. 05) , and the remission stage group also had significantly higher expression rates than the control group (both P < 0. 05) . There were gradual increases in the expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells in the patients with type 1 AIH in G0 group (7. 88% ± 3. 85% and 5. 36% ±3. 12%) , G1-2 group (10. 13% ± 4. 74% and 10. 45% ± 4. 34%) , and G3-4 group (15. 63% ± 5. 98% and 14. 73% ± 5. 12%) (χ2=12. 14 and 10. 32, P < 0. 05) . In the patients in the active stage of type I AIH, the expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells were positively correlated with total bilirubin, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, and immunoglobulin G (CD4+T cells: r = 0. 687, 0. 736, 0. 702, 0. 647, and 0. 824, all P < 0. 01; CD8+T cells: r = 0. 673, 0. 719, 0. 680, 0. 631, and 0. 817, all P < 0. 01) ; the expression rates of PD-L1 on the surface of peripheral blood CD4+and CD8+T cells were also positively correlated with liver inflammation grade (rs= 0. 768 and 0. 721, both P < 0. 05) . Conclusion In patients with type I AIH, high expression of PD-L1 on peripheral blood T cells is closely associated with liver inflammation grade, suggesting that PD-L1 may be involved in the development and progression of type 1 AIH.
- hepatitis, autoimmune /
- T-lymphocytes /
- programmed death-ligand 1

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参考文献(15)

[1]KRAWITT EL.Autoimmune hepatitis[J].N Eng I J Med, 2006, 354 (1) :54-66.

[2]LIBERAL R, LONGHI MS, MIELI-VERGANI G, et al.Pathogenesis of autoimmune hepatitis[J].Best Pract Res Clin Gastroenterol, 2011, 25 (6) :653-664.

[3]FRANCISCO LM, SAGE PT, SHARPE AH.The PD-1 pathway in tolerance and autoimmunity[J].Immunol Rev, 2010, 236 (7) :219-242.

[4]HERMES EM, ZENIYA M, CZAJA AJ, et al.Simplified criteria for the diagnosis of autoimmune hepatitis[J].Hepatology, 2008, 48 (1) :169-176.

[5]MANNS MP, CZAJA AJ, GORHAM JD, et al.Diagnosis and management of auto-immune hepatitis[J].Hepatology, 2010, 51 (6) :2193-2213.

[6]KAMIJO A, YOSHIZAWA K, JOSHITA S, et al.Cytokine profiles affecting the pathogenesis of autoimmune hepatitis in Japanese patients[J].Hepatol Res, 2011, 41 (4) :350-357.

[7]LI YN, ZHOU L, ZHANG J, et al.Chronological changes in clinical features of autoimmune liver disease at initial diagnosis[J].J Clin Hepatol, 2017, 33 (1) :141-145. (in Chinese) 李燕妮, 周璐, 张洁, 等.自身免疫性肝病首诊临床特征的年代变迁[J].临床肝胆病杂志, 2017, 33 (1) :141-145.

[8]SHI F, SHI M, ZHEN Z, et al.PD-1 and PD-L1 upregulation promotes CD8 (+) T-cell apoptosis and postoperative recurrence in hepatocellular carcinoma patients[J].Int J Cancer, 2011, 128 (4) :887-896.

[9]SALAMA AD, CHITNIS T, IMITOLA J, et al.Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis[J].J Exp Med, 2003, 198 (1) :71-78.

[10]FIFE BT, GULERIA I, BUPP MG, et al.Insulin-induced remission in new-onset NOD mice is maintained by the PD-1/PD-L1pathway[J].J Exp Med, 2006, 203 (12) :2737-2747.

[11]SARESELLA M, RAINONE V, AI-DAGHRI NM, et al.The PD-1/PD-L1 pathway in human pathology[J].Curr Mol Med, 2012, 12 (3) :259-267.

[12]MIYAKE Y, YAMAMOTO K, MATSUSHITA H, et al.Multicenter validation study of anti-programmed cell death-1 antibody as a serological marker for type 1 autoimmune hepatitis[J].Hepatol Res, 2014, 44 (13) :1299-1307.

[13]MATSUMOTO K, MIYAKE Y, MATSUSHITA H, et al.Antiprogrammed cell death-1 antibody as a new serological marker for type 1 autoimmune hepatitis[J].J Gastroenterol Hepatol, 2014, 29 (1) :110-115.

[14]KE KY, XIONG KG, WEI DH, et al.Expression of programmed cell death ligand 1 in liver tissue and its correlation with liver function of patients with autoimmune hepatitis[J].Chin J Infect Dis, 2016, 34 (10) :577-581. (in Chinese) 柯坤宇, 熊克宫, 魏大海, 等.自身免疫性肝炎患者肝组织程序性细胞死亡因子配体1的表达及其与肝功能的相关性[J].中华传染病杂志, 2016, 34 (10) :577-581.

[15]LI Y, KILANI RT, PAKYARI M, et al.Increased expression of PD-L1 and PD-L2 in dermal fibroblasts from alopecia areata mice[J].J Cell Physiol, 2018, 233 (3) :2590-2601.

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