Expression and clinical significance of TIGIT, CD226, CD96, and CD155 in platelet glycoprotein autoantibody-positive primary immune thrombocytopenia
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摘要: 目的 探讨TIGIT、CD226、CD96和CD155在血小板糖蛋白自身抗体(platelet glycoprotein autoantibody，GPs)阳性的原发性免疫性血小板减少症(immune thrombocytopenia，ITP)患者外周血CD8+T细胞和树突状细胞(dendritic cell，DC)膜表面的表达，并分析其临床意义。方法 选取41例GPs阳性的ITP患者和20例健康对照者，采用流式细胞术检测CD8+T细胞表面TIGIT、CD226和CD96表达比例，并检测ITP患者外周血DC细胞的亚群变化及浆细胞样DC(plasma DC，pDC)上CD155的表达比例。结果 GPs阳性ITP组患者的pDC和CD155+pDC比例均明显高于对照组，且GPⅠb/Ⅸ+/Ⅱb/Ⅲa+/-组均明显高于GPⅠb/Ⅸ-/Ⅱb/Ⅲa+组(P < 0.05，F=40.83；P < 0.01，F=59.50)。GPs阳性ITP组患者的TIGIT+CD8+T细胞比例明显低于对照组，且GPⅠb/Ⅸ+/Ⅱb/Ⅲa+/-组明显低于GPⅠb/Ⅸ-/Ⅱb/Ⅲa+组(P < 0.05，F=36.41)，但CD226+CD8+T细胞与CD96+CD8+T细胞比例均明显高于对照组，且GPⅠb/Ⅸ+/Ⅱb/Ⅲa+/-组均明显高于GPⅠb/Ⅸ-/Ⅱb/Ⅲa+组(P < 0.05，F=45.01；P < 0.01，F=41.66)。GPⅠb/Ⅸ-/Ⅱb/Ⅲa+组与GPⅠb/Ⅸ+/Ⅱb/Ⅲa+/-组的CD155+pDC与TIGIT+CD8+T细胞比例呈负相关(P < 0.01，r=-0.54；P < 0.01，r=-0.76)，与CD226+CD8+T细胞和CD96+CD8+T细胞比例呈正相关(P < 0.05，r=0.61；P < 0.05，r=0.51；P < 0.01，r=0.79；P < 0.01，r=0.73)。结论 TIGIT、CD226、CD96与CD155表达异常，导致GPs阳性的ITP的免疫失耐受，可能参与了疾病发生。Abstract: Objective To investigate the expression of TIGIT, CD226, CD96 and CD155 on CD8+T cells and dendritic cells(DC) in the peripheral blood of patients with platelet glycoprotein autoantibody(GPs) -positive primary immune thrombocytopenia(ITP) and to analyze their clinical significance.Methods Forty-one GP-positive ITP patients and 20 healthy individuals were selected. The flow cytometry was used to detect the percentage of TIGIT, CD226, and CD96 expression on CD8+T cells and the changes in DC cell subsets and the percentage of CD155 expression on plasma DC(pDC) were analyzed.Results The percentage of pDC and CD155+pDC in the GPs-positive ITP group were significantly higher than those in the healthy control group, and they were significantly higher in the GPⅠb/Ⅸ+/Ⅱb/Ⅲa+/-group than those in the GPⅠb/Ⅸ-/Ⅱb/Ⅲa+group(P < 0.05, F=40.83; P < 0.01, F=59.50). On the other hand, the percentage of TIGIT+CD8+T cells in the GPs-positive ITP group was significantly lower than that in the healthy control group, and it was significantly lower in the GPⅠb/Ⅸ+/Ⅱb/Ⅲa+/-group than that in the GPⅠb/Ⅸ-/Ⅱb/Ⅲa+group(P < 0.05, F=36.41). However, the percentages of CD226+CD8+T cells and CD96+CD8+T cells were significantly higher than those in the control group, and they were significantly higher in the GPⅠb/Ⅸ+/Ⅱb/Ⅲa+/-group than those in the GPⅠb/Ⅸ-/Ⅱb/Ⅲa+group(P < 0.05, F=45.01; P < 0.01, F=41.66). The percentages of CD155+pDC in the GPⅠb/Ⅸ-/Ⅱb/Ⅲa+group and GPⅠb/Ⅸ+/Ⅱb/Ⅲa+/-group were negatively correlated with TIGIT+CD8+T cells(P < 0.01, r=-0.54; P < 0.01, r=-0.76), while it positively correlated with the percentages of CD226+CD8+T cells and CD96+CD8+T cells(P < 0.05, r=0.61; P < 0.05, r=0.51; P < 0.01, r=0.79; P < 0.01, r=0.73).Conclusion The abnormal expression of TIGIT, CD226, CD96, and CD155 contributes to immune intolerance in GPs-positive ITP, which may be involved in the pathogenesis of the disease.
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Key words:
- immune thrombocytopenia /
- inhibitory molecule /
- CD226 /
- CD96
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表 1 GPⅠb/Ⅸ+/Ⅱb/Ⅲa-组与GPⅠb/Ⅸ+/Ⅱb/Ⅲa+组DC亚群、CD155+pDC和CD226+/TIGIT+/CD96+CD8+T细胞比例的比较
组别 例数 pDC/% mDC/% CD155+pDC/% CD226+
CD8+T/%TIGIT+
CD8+T/%CD96+
CD8+T/%GPⅠb/Ⅸ+/Ⅱb/Ⅲa-组 13 18.82
(16.32，21.02)46.93
(44.32，58.51)21.75
(19.86，25.32)27.31
(26.21，29.32)7.49
(5.69，15.36)13.21
(12.65，15.65)GPⅠb/Ⅸ+/Ⅱb/Ⅲa+组 5 19.03
(18.96，19.03)51.63
(44.18，57.82)22.01
(17.48，25.41)27.32
(22.23，30.28)8.21
(4.95，13.65)14.23
(10.94，15.48)Z -0.093 -0.246 -0.049 -0.542 -0.197 -0.187 P 0.926 0.805 0.961 0.588 0.844 0.766 
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