sPD-1/sPD-L1与Th1/Th2及Th17/Treg相关细胞因子在原发免疫性血小板减少症中的研究
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摘要
目的:探讨原发免疫性血小板减少症(ITP)中s PD-1/s PD-L1的表达情况及其与Th1/Th2、Th17/Treg的平衡关系。方法:采用酶联免疫吸附试验(ELISA)分别检测35例初诊ITP患者和20例健康体检者外周血血清中s PD-1、s PD-L1、IFN-γ、IL-4、IL-17、TGF-β的水平。结果:①与正常对照组相比,ITP患者s PD-1、IFN-γ、IL-17水平升高(P=0. 008、P=0. 031、P=0. 005),IL-4、TGF-β水平降低(P=0. 028、P=0. 042),s PD-L1水平无明显变化(P=0. 107)。②Pearson相关性分析显示:s PD-1与IFN-γ呈正相关(r=0. 516,P=0. 006),与血小板计数呈负相关(r=-0. 562,P=0. 002);血小板计数与IFN-γ呈负相关(r=-0. 531,P=0. 004); s PD-1与IL-4、IL-17、TGF-β无相关性(P均>0. 05)。结论:s PD-1可能通过抑制PD-1/PD-L1负性调节通路,导致T亚群失衡,在ITP疾病中发挥一定的作用。
Objective: To investigate the expression of s PD-1/s PD-L1 and its balance relationship with Th1/Th2,Th17/Treg in primary immune thrombocytopenia( ITP). Methods: The levels of s PD-1,s PD-L1,IFN-γ,IL-4,IL-17 and TGF-β were detected in 35 patients with initial diagnosis of ITP and 20 healthy subjects by enzyme-linked immunosorbent assay( ELISA). Results: ①Compared with the normal control group,the level of s PD-1,IFN-γ and IL-17 in ITP patients increased( P = 0. 008,P = 0. 031,P = 0. 005),and IL-4 and TGF-β were decreased( P = 0. 028,P = 0. 042),and no significant change in s PD-L1 level( P = 0. 107). ②The correlation analysis showed that s PD-1 was positively correlated with IFN-γ( r = 0. 516,P = 0. 006),negatively correlated with platelet count( r =-0. 562,P = 0. 002). The platelet count was negatively correlated with IFN-γ( r =-0. 531,P = 0. 004). There was no correlation betweens PD-1 and IL-4,IL-17 and TGF-β( P>0. 05). Conclusion: s PD-1 may inhibit the PD-1/PD-L1 negative regulation pathway and lead to the imbalance of T cells subgroups and play an important role in ITP disease.
Objective: To investigate the expression of s PD-1/s PD-L1 and its balance relationship with Th1/Th2,Th17/Treg in primary immune thrombocytopenia( ITP). Methods: The levels of s PD-1,s PD-L1,IFN-γ,IL-4,IL-17 and TGF-β were detected in 35 patients with initial diagnosis of ITP and 20 healthy subjects by enzyme-linked immunosorbent assay( ELISA). Results: ①Compared with the normal control group,the level of s PD-1,IFN-γ and IL-17 in ITP patients increased( P = 0. 008,P = 0. 031,P = 0. 005),and IL-4 and TGF-β were decreased( P = 0. 028,P = 0. 042),and no significant change in s PD-L1 level( P = 0. 107). ②The correlation analysis showed that s PD-1 was positively correlated with IFN-γ( r = 0. 516,P = 0. 006),negatively correlated with platelet count( r =-0. 562,P = 0. 002). The platelet count was negatively correlated with IFN-γ( r =-0. 531,P = 0. 004). There was no correlation betweens PD-1 and IL-4,IL-17 and TGF-β( P>0. 05). Conclusion: s PD-1 may inhibit the PD-1/PD-L1 negative regulation pathway and lead to the imbalance of T cells subgroups and play an important role in ITP disease.
引文
[1]中华医学会血液学分会止血与血栓学组.成人原发免疫性血小板减少症诊断与治疗中国专家共识(2016年版)[J].中华血液学杂志,2016,37(2):89-93.Thrombosis and Hemostasis Group,Hematology Societ,Chinese Medical Association.Consensus of Chinese experts on diagnosis and treatment of adult primary immune thrombocytopenia(version2016)[J].Chin J Hematol,2016,37(2):89-93.
[2]Zhang J,Zhang Q,Li Y,et al.Immune dysregulation in primary immune thrombocytopenia patients[J].Hematology,2018,6:1-7.
[3]冯媛,耿玲玲,李小青,等.MicroRNA-15a在儿童原发性免疫性血小板减少症中的表达及其意义[J].中国实验血液学杂志,2017,25(6):1772-1775.Feng Y,Geng LL,Li XQ,et al.Expression of MicroRNA-15a in children with primary immune thrombocytopenia and its significance[J].Chin J Exp Homatol,2017,25(6):1772-1775.
[4]王秀娟,赵芳,刘颖,等.辅助型T细胞相关因子在特发性血小板减少性紫癜模型小鼠中的变化和意义[J].血栓与止血学,2017,23(6):901-903,907.Wang XJ,Zhao F,Liu Y,et al.Changes and significance of T helper cell related cytokines in ITP mouse model[J].Chin J Thromb Hemos,2017,23(6):901-903,907.
[5]Liu C,Jiang J,Gao L,et al.Soluble PD-1 aggravates progression of collagen-induced arthritis through Th1 and Th17 pathways[J].Arthritis Res Therapy,2015,17:340.
[6]Fukasawa T,Yoshizaki A,Ebata S,et al.Contribution of soluble forms of programmed death-1 and programmed death ligand 2 to disease severity and progression in systemic sclerosis[J].Arthritis Rheumatol,2017,69(9):1879-1890.
[7]Aarslev K,Dige A,Greisen SR,et al.Soluble programmed death-1levels are associated with disease activity and treatment response in patients with autoimmune hepatitis[J].Scand J Gastroenterol,2017,52(1):93-99.
[8]翟菊萍,何杨,杨炳华.免疫失耐受在ITP自身抗体产生机制中的研究进展[J].中华微生物学和免疫学杂志,2016,36(10):790-794.Zhai JP,He Y,Yang BH.Mechanisms of loss of immune tolerance in the production of antiplatelet autoantibodies in primary immune thrombocytopenia[J].Chin J Microbiol Immunol,2016,36(10):790-794.
[9]Li Y,Xiao Y,Su M,et al.Role of soluble programmed death-1(s PD-1)and s PD-ligand 1 in patients with cystic echinococcosis[J].Exp Ther Med,2016,11(1):251-256.
[10]Nan J,Liang L,Li L,et al.Soluble programmed death-1 and soluble programmed death ligand 1 protein expression and immune status in patients with recurrent aphthous ulcer[J].West China JStomatol,2017,35(3):286-290.
[11]Wang Y,Pang N,Wang X,et al.Percentages of PD-1+CD4+Tcells and PD-L1+DCs are increased and s PD-1 level is elevated in patients with immune thrombocytopenia[J].Human Vaccines Immunotherap,2018,14(4):832-838.
[12]Yazdanbakhsh K,Zhong H,Bao W.Immune dysregulation in immune thrombocytopenia[J].Semin Hematol,2013,50(1):63-67.
[13]罗洪强,封蔚莹,钟永根,等.CBA技术检测ITP患者Th1/Th2细胞因子平衡偏移的临床意义[J].中国实验血液学杂志,2016,24(6):1846-1849.Luo HQ,Feng WY,Zhoug YG,et al.Clinical significance of the balanceshift of Th1 and Th2 type cytokines in patients with primary immune thrombocytopenic purpura detected by cytometric bead array[J].Chin J Cell Mol Immunol,2016,24(6):1846-1849.
[14]郭新红,赵芳,石伟,等.特发性血小板减少性紫癜患者Th1/Th2的细胞因子水平及临床意义[J].细胞与分子免疫学杂,2012,28(11):1185-1187.Guo XH,Zhao F,Shi W,et al.Detection and clinical significance of Th1/Th2 cytokines in patients with idiopathic thrombocypenic purpura[J].Chin J Cell Mol Immunol,2012,28(11):1185-1187.
[15]王志高,哈力达·亚森,赵芳,等.原发免疫性血小板减少症患者CD4+T细胞CD28的表达及其与IFN-γ/IL-10比率的关系[J].细胞与分子免疫学杂,2013,29(8):850-853.Wang ZG,Halida YS,Zhao F,et al.CD28 expression on CD4(+)T cells and its relationship with IFN-γ/IL-10 ratio in patients with primary immune thrombocytopenia[J].Chin J Cell Mol Immunol,2013,29(8):850-853.
[16]Zhang J,Ma D,Zhu X,et al.Elevated profile of Th17,Th1 and Tc1 cells in patients with immune thrombocytopenic purpura[J].Haematologica,2009,94(9):1326-1329.
[17]张萍,刘红云,刘晓燕,等.调节性T细胞在小鼠ITP发病中的作用[J].中国实验血液学杂志,2016,24(3):784-787.Zhang P,Liu HY,Liu XY,et al.Role of Treg cells in pathogensis of mouse ITP[J].Chin J Exp Hematol,2016,24(3):784-787.
[18]Ren CF,Zhao YX,Hou CF,et al.Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression[J].Mol Med Rep,2017,15(1):460-466.
[2]Zhang J,Zhang Q,Li Y,et al.Immune dysregulation in primary immune thrombocytopenia patients[J].Hematology,2018,6:1-7.
[3]冯媛,耿玲玲,李小青,等.MicroRNA-15a在儿童原发性免疫性血小板减少症中的表达及其意义[J].中国实验血液学杂志,2017,25(6):1772-1775.Feng Y,Geng LL,Li XQ,et al.Expression of MicroRNA-15a in children with primary immune thrombocytopenia and its significance[J].Chin J Exp Homatol,2017,25(6):1772-1775.
[4]王秀娟,赵芳,刘颖,等.辅助型T细胞相关因子在特发性血小板减少性紫癜模型小鼠中的变化和意义[J].血栓与止血学,2017,23(6):901-903,907.Wang XJ,Zhao F,Liu Y,et al.Changes and significance of T helper cell related cytokines in ITP mouse model[J].Chin J Thromb Hemos,2017,23(6):901-903,907.
[5]Liu C,Jiang J,Gao L,et al.Soluble PD-1 aggravates progression of collagen-induced arthritis through Th1 and Th17 pathways[J].Arthritis Res Therapy,2015,17:340.
[6]Fukasawa T,Yoshizaki A,Ebata S,et al.Contribution of soluble forms of programmed death-1 and programmed death ligand 2 to disease severity and progression in systemic sclerosis[J].Arthritis Rheumatol,2017,69(9):1879-1890.
[7]Aarslev K,Dige A,Greisen SR,et al.Soluble programmed death-1levels are associated with disease activity and treatment response in patients with autoimmune hepatitis[J].Scand J Gastroenterol,2017,52(1):93-99.
[8]翟菊萍,何杨,杨炳华.免疫失耐受在ITP自身抗体产生机制中的研究进展[J].中华微生物学和免疫学杂志,2016,36(10):790-794.Zhai JP,He Y,Yang BH.Mechanisms of loss of immune tolerance in the production of antiplatelet autoantibodies in primary immune thrombocytopenia[J].Chin J Microbiol Immunol,2016,36(10):790-794.
[9]Li Y,Xiao Y,Su M,et al.Role of soluble programmed death-1(s PD-1)and s PD-ligand 1 in patients with cystic echinococcosis[J].Exp Ther Med,2016,11(1):251-256.
[10]Nan J,Liang L,Li L,et al.Soluble programmed death-1 and soluble programmed death ligand 1 protein expression and immune status in patients with recurrent aphthous ulcer[J].West China JStomatol,2017,35(3):286-290.
[11]Wang Y,Pang N,Wang X,et al.Percentages of PD-1+CD4+Tcells and PD-L1+DCs are increased and s PD-1 level is elevated in patients with immune thrombocytopenia[J].Human Vaccines Immunotherap,2018,14(4):832-838.
[12]Yazdanbakhsh K,Zhong H,Bao W.Immune dysregulation in immune thrombocytopenia[J].Semin Hematol,2013,50(1):63-67.
[13]罗洪强,封蔚莹,钟永根,等.CBA技术检测ITP患者Th1/Th2细胞因子平衡偏移的临床意义[J].中国实验血液学杂志,2016,24(6):1846-1849.Luo HQ,Feng WY,Zhoug YG,et al.Clinical significance of the balanceshift of Th1 and Th2 type cytokines in patients with primary immune thrombocytopenic purpura detected by cytometric bead array[J].Chin J Cell Mol Immunol,2016,24(6):1846-1849.
[14]郭新红,赵芳,石伟,等.特发性血小板减少性紫癜患者Th1/Th2的细胞因子水平及临床意义[J].细胞与分子免疫学杂,2012,28(11):1185-1187.Guo XH,Zhao F,Shi W,et al.Detection and clinical significance of Th1/Th2 cytokines in patients with idiopathic thrombocypenic purpura[J].Chin J Cell Mol Immunol,2012,28(11):1185-1187.
[15]王志高,哈力达·亚森,赵芳,等.原发免疫性血小板减少症患者CD4+T细胞CD28的表达及其与IFN-γ/IL-10比率的关系[J].细胞与分子免疫学杂,2013,29(8):850-853.Wang ZG,Halida YS,Zhao F,et al.CD28 expression on CD4(+)T cells and its relationship with IFN-γ/IL-10 ratio in patients with primary immune thrombocytopenia[J].Chin J Cell Mol Immunol,2013,29(8):850-853.
[16]Zhang J,Ma D,Zhu X,et al.Elevated profile of Th17,Th1 and Tc1 cells in patients with immune thrombocytopenic purpura[J].Haematologica,2009,94(9):1326-1329.
[17]张萍,刘红云,刘晓燕,等.调节性T细胞在小鼠ITP发病中的作用[J].中国实验血液学杂志,2016,24(3):784-787.Zhang P,Liu HY,Liu XY,et al.Role of Treg cells in pathogensis of mouse ITP[J].Chin J Exp Hematol,2016,24(3):784-787.
[18]Ren CF,Zhao YX,Hou CF,et al.Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells and its effects on rheumatoid arthritis progression[J].Mol Med Rep,2017,15(1):460-466.