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)%、(11.13±4.63)%]均高于缓解期[(7.88±3.85)%、(7.36±3.12)%]和对照组[(5.42±2.64)%、(4.86±2.16)%](F值分别为15.76、13.54,P值均<0.05),且缓解期组亦均高于对照组(P值均<0.05)。1型AIH患者外周血CD4+、CD8+T淋巴细胞表面PD-L1的表达率在G0组[(7.88±3.85)%、(5.36±3.12)%]、G1~2组[(10.13±4.74)%、(10.45±4.34)%]及G3~4组[(15.63±5.98)%、(14.73±5.12)%]逐渐升高(χ2值分别为12.14、10.32,P值均<0.05)。1型活动期AIH患者外周血CD4+、CD8+T淋巴细胞表面PD-L1的表达率与TBil、ALT、AST、GGT及Ig G水平均呈正相关(CD4+T淋巴细胞:r值分别为0.687、0.736、0.702、0.647、0.824;CD8+T淋巴细胞r值分别为0.673、0.719、0.680、0.631、0.817,P值均<0.01),且1型AIH患者外周血CD4+、CD8+T淋巴细胞表面PD-L1的表达率与肝组织炎症活动度分级亦均呈正相关(rs值分别为0.768、0.721,P值均<0.05)。结论 1型AIH患者外周血T淋巴细胞PD-L1高表达与肝组织炎症活动密切相关,提示PD-L1可能参与了1型AIH的发生发展。
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.
作者
熊克宫
柯坤宇
孔金峰
柳丽娟
陈丽芳
林小钦
XIONG Kegong;KE Kunyu;KONG Jinfeng(Department of Liver Diseases,Mengchao Hepatobiliary Hospital of Fujian Medical University ＆ Affiliated Infectious Diseases Hospital of Fujian Medical University,Fuzhou 350025,China)
出处
《临床肝胆病杂志》
CAS
北大核心
2018年第6期1248-1252,共5页
Journal of Clinical Hepatology
基金
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)
作者简介
熊克宫（1982-），男，主要从事肝病相关研究。;通信作者：陈丽芳，电子信箱：42255769@qq．com。
