Tfh细胞上TIGIT和PD-1共表达在慢性淋巴细胞白血病患者外周血中的变化特点及意义

The changes and significance of TIGIT and PD-1 co-expression on Tfh cells in peripheral blood of patients with chronic lymphocytic leukemia

目的:初步探讨慢性淋巴细胞白血病(chronic lymphocytic leukemia,CLL)患者外周血共抑制分子T细胞免疫球蛋白和ITIM结构域(T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain,TIGIT)和程序性细胞死亡受体1(programmed cell death protein 1,PD-1)在Tfh细胞上的表达变化特点及临床意义。方法:采用流式细胞术检测50例CLL患者、36例非CLL的慢性B淋巴细胞增殖疾病患者和30例健康者外周血Tfh细胞百分比和Tfh细胞上PD-1和TIGIT的水平,比较3组受试者的差异。分析CLL患者TIGIT+PD-1+Tfh细胞百分比与IPI评分分层的关系,以及与免疫球蛋白的相关性。结果:(1)与对照组比较,初诊CLL患者Tfh、PD-1+Tfh、TIGIT+Tfh、TIGIT+PD-1+Tfh、TIGIT+PD-1-Tfh和TIGIT-PD-1+Tfh细胞百分比明显增高,差异有统计学意义(P<0.05)。(2)TIGIT+PD-1+Tfh细胞在CLL-IPI预后分层低危组、中危组、高危组、极高危组比较分析结果,组间和组内两两比较差异均有统计学意义(P<0.05),随着预后分层增加TIGIT+PD-1+Tfh细胞水平逐渐增加。(3)受试者工作特征曲线结果显示,TIGIT+PD-1+Tfh细胞在CLL患者和非CLL患者的鉴别诊断中具有一定的诊断价值(P<0.05)。(4)Logistic回归分析显示,TIGIT+PD-1+Tfh细胞百分比是CLL发病的独立危险因素(P<0.05)。(5)CLL患者外周血中TIGIT+PD-1+Tfh与IgA、IgM、IgG均呈负相关(P<0.05)。结论:初诊CLL患者外周血TIGIT+PD-1+Tfh细胞百分比明显增加,Tfh细胞高表达共抑制分子TIGIT和PD-1参与CLL疾病的发生,并且与疾病的免疫球蛋白水平降低有关。

Objective To investigate the expression and clinical significance of T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain(TIGIT)and programmed cell death protein 1(PD-1)on T follicular helper cells(Tfh)in peripheral blood of patients with chronic lymphocytic leukemia(CLL).Methods The percentage of peripheral blood Tfh cells and the levels of PD-1 and TIGIT were measured by flow cytometry in 50 CLL patients,36 chronic B lymphocyte proliferation disease patients without CLL,and 30 healthy individuals.The differences among the three groups of subjects were compared.The percentage of TIGIT+PD-1+Tfh cells in CLL patients was analyzed in relation to IPI score stratification,as well as correlation with immunoglobulins.Results①Compared with healthy controls,the percentages of Tfh,PD-1+Tfh,TIGIT+Tfh,TIGIT+PD-1+Tfh,TIGIT+PD-1-Tfh and TIGIT-PD-1+Tfh cells were significantly higher in newly diagnosed CLL patients(P<0.05).②The results of comparative analysis of TIGIT+PD-1+Tfh cells in CLL-IPI prognostic stratification low-risk,intermediate-risk,high-risk,and very high-risk groups showed that there were significant differences between and within groups(P<0.05),and TIGIT+PD-1+Tfh cell levels gradually increased with increasing prognostic stratification.③The results of receiver operating characteristic curve showed that TIGIT+PD-1+Tfh cells had certain diagnostic value in the differential diagnosis of CLL patients and non-CLL patients(P<0.05).④Logistic regression analysis showed that the percentage of TIGIT+PD-1+Tfh cells was an independent risk factor for CLL(P<0.05).⑤TIGIT+PD-1+Tfh was negatively correlated with IgA,IgM,and IgG levels in the peripheral blood of CLL patients(P<0.05).Conclusion The percentage of TIGIT+PD-1+Tfh cells in peripheral blood of newly diagnosed CLL patients is significantly increased.TIGIT and PD-1,which are highly expressed in Tfh cells,are involved in the occurrence of CLL diseases and are associated with decreased immunoglobulin levels in the diseases.