【摘要】 目的观察4种免疫抑制因子〔程序性死亡受体-1(PD-1)、程序性死亡受体-1配体(PD-L1)、细胞毒性T淋巴细胞相关抗原-4(CTLA-4)、含T细胞免疫球蛋白和ITIM结构域蛋白(TIGIT)〕在传染性单核细胞增多症(IM)B淋巴细胞上的表达水平及临床意义。方法以2017年4月—9月湖南省儿童医院收治的IM患者为研究对象(IM组),急性期59例,恢复期34例,20例健康体检儿童为正常对照组。采用流式细胞术分别检测PD-1、PD-L1、CTLA-4、TIGIT在各组B淋巴细胞上的表达水平及急性期表达量与血浆/血清EBV-DNA含量的相关性。结果与正常对照组比较,IM急性期组患者的PD-1、PD-L1、CTLA-4、TIGIT在B细胞上均显著升高〔PD-1:5.22(3.15)%比0.76(0.86)%,PD-L1:7.80(5.29)%比0.87(0.09)%,CTLA-4:4.23(6.21)%比0.52(0.28)%,TIGIT:9.78(5.72)%比2.23(1.05)%,均P<0.05〕。IM恢复期组PD-L1、TIGIT在B细胞上的表达较正常对照组明显升高〔PD-L1:4.43(6.27)%比0.87(0.09)%,TIGIT:6.03(5.46)%比2.23(1.05)%,均P<0.05〕,但其升高程度明显低于急性期组(均P<0.05)。对急性期59例患者抽血查EBV-DNA检测结果为(8.44±2.04)×10~5拷贝/mL。相关性分析显示,IM患者急性期TIGIT在B细胞上表达水平与EBV-DNA含量呈正相关(r=0.371,P=0.006);而其余3个指标则无相关性,PD-1:r=0.049,P=0.723;PD-L1:r=0.068,P=0.625;CTLA-4:r=0.662,P=0.659。结论 PD-1、PD-L1、CTLA-4、TIGIT在IM急性期表达上调,随着疾病恢复而表达有所下降,提示在IM发病中有一定作用;同时急性期TIGIT表达水平与血浆/血清EBV-DNA含量高低有关。更多还原

【Abstract】 Objective To observe the expression and clinical significance of four immunosuppressive factors [programmed death 1 (PD-1),programmed death 1 ligand (PD-L1),cytotoxic T lymphocyte antigen 4 (CTLA-4) and T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory domains (TIGIT)] in B lymphocytes of patients with infectious mononucleosis (IM).Methods The IM patients admitted to the Hunan Children’s Hospital from April 2017 to September 2017 were selected as research objects,including 59 cases in acute phase,34 cases in recovery phase,and 20 healthy children as control group.Flow cytometry was used to detect the expression levels of PD-1,PD-L1,CTLA-4 and TIGIT in B lymphocytes of each group,and the correlation between the expression in acute phase and the contents of EBV-DNA in plasma/serum.Results Compared with the control group,PD-1,PD-L1,CTLA-4 and TIGIT were significantly increased on B cells in the acute phase of IM [PD-1:5.22 (3.15)% vs.0.76 (0.86)%,PD-L1:7.80 (5.29)% vs.0.87 (0.09)%,CTLA-4:4.23 (6.21)% vs.0.52 (0.28)%,TIGIT:9.78 (5.72)% vs.2.23 (1.05)%,all P < 0.05].During the IM recovery phase,PD-L1 and TIGIT were obviously elevated on B cells [PD-L1:4.43 (6.27)% vs.0.87 (0.09)%,TIGIT:6.03 (5.46)% vs.2.23 (1.05)%,P < 0.05],However,the degree of increase was significantly lower than that of acute stage,both P < 0.05.The EBV-DNA test results of 59 patients in acute phase were (8.44±2.04)×10~5 copy/mL.The correlation analysis showed that in the acute phase of IM patients the expression level of TIGIT on B cells was positively correlated with EBV-DNA content (r=0.371,P=0.006),while there was no correlation among the other 3 indexs (PD-1:r=0.049,P=0.723;PD-L1:r=0.068,P=0.625;CTLA-4:r=0.662,P=0.659).Conclusions PD-1,PD-L1,CTLA-4 and TIGIT are up-regulated in the acute phase of the disease,and the expression decreases with the recovery of the disease.This study suggests that it may be involved in the pathogenesis of IM.At the same time,the expression level of TIGIT in acute phase is positively correlated with EBV-DNA content in plasma/serum.更多还原