免疫性血小板减少症患者调节性B细胞变化与临床意义
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摘要
目的:本研究旨在探讨调节B细胞(Breg)在免疫性血小板减少症(ITP)发病中的作用及其临床意义。方法:采用流式细胞术检测40例ITP患者(ITP组)的Breg、Th1、Th2、Th17以及Treg细胞的细胞量,应用AimPlex流式高通量技术检测IL-10、TGF-β、CD40以及CD40L的水平,选择20例健康正常人作为对照(对照组)。结果:与对照组相比较,ITP患者Breg细胞的细胞数量显著少于对照组(P <0.05),IL-10、TGF-β以及CD40L的水平亦显著低于对照组(P <0.05)。Th1细胞数量显著增多(P <0.05),而Th2、Th17以及Treg细胞量均显著减少(P <0.05)。结论:Breg细胞在ITP发病机制中可能具有重要作用。
Objective: To investigate the role of regulatory B cells(Breg) in pathogenesis of immune thrombocytopenia(ITP) and its clinical significance. Methods: A total of 40 ITP patients and 20 normal controls were enrolled in this study. The content of Breg, Th1, Th2, Th17 and Treg cells were detected by flow cytometry(FCM). The expression level of IL-10, TGF-β, CD40 and CD40 L was detected by AimPlex Flow High Throughput Screening Technology. Results: The of Breg cells in ITP patients was significantly lower than that in normal controls(P <0.05),the expression levels of IL-10, TGF-β and CD40 L in ITP patients were also significantly lower than those in normal controls(P <0.05). The contents of Th1 cells in ITP patients were significantly higher than that in normal controls(P <0.05), whereas the contents of Th2, Th17 and Treg cells in ITP patients were significantly lower than those in normal controls(P <0.05). Conclusion: The Breg cells may play an important role in the pathogenesis of ITP.
Objective: To investigate the role of regulatory B cells(Breg) in pathogenesis of immune thrombocytopenia(ITP) and its clinical significance. Methods: A total of 40 ITP patients and 20 normal controls were enrolled in this study. The content of Breg, Th1, Th2, Th17 and Treg cells were detected by flow cytometry(FCM). The expression level of IL-10, TGF-β, CD40 and CD40 L was detected by AimPlex Flow High Throughput Screening Technology. Results: The of Breg cells in ITP patients was significantly lower than that in normal controls(P <0.05),the expression levels of IL-10, TGF-β and CD40 L in ITP patients were also significantly lower than those in normal controls(P <0.05). The contents of Th1 cells in ITP patients were significantly higher than that in normal controls(P <0.05), whereas the contents of Th2, Th17 and Treg cells in ITP patients were significantly lower than those in normal controls(P <0.05). Conclusion: The Breg cells may play an important role in the pathogenesis of ITP.
引文
1王明镜,胡晓梅,邓中阳,等.免疫性血小板减少症的免疫机制研究进展.临床血液学杂志,2017;9(5):725-728.
2 Gudbrandsdottir S,Ghanima W,Nielsen CH,et al.Effect of thrombopoietin-receptor agonists on circulating cytokine and chemokine levels in patients with primary immune thrombocytopenia(ITP).Platelets,2017;28(5):478-483.
3中华医学会血液学分会血栓与止血学组.成人原发免疫性血小板减少症诊断与治疗中国专家共识(2012年版).中华血液学杂志,2012;33(11):975-977.
4 Wolf SD,Dittel BN,Hardardottir F,et al.Experimental autoimmune encephalomyelitis induction in genetically B cell deficient mice.JExp Med,1996;184(6):2271-2278.
5 Mizoguchi A,Mizoguchi E,Takedatsu H,et al.Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation.Immunity,2002;16(2):219-230.
6 Mizoguchi A,Bhan AK.A case for regulatory B cells.J Immunol,2006;176(2):705-710.
7 Mauri C,Bosma A.Immune regulatory function of B cells.Annu Rev Immunol,2012;30:221-241.
8 Blair PA,Norena LY,Flores-Borja F,et al.CD19+CD24hiCD38hi cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients.Immunity,2010;32(1):129-140.
9 Noh J,Choi WS,Noh S,et al.Presence of foxp3-expressing CD19+CD5+B cells in human peripheral blood mononuclear cells:human CD19+CD5+foxp3+regulatory B cell(Breg).Immune Netw,2010;10(6):247-249.
10李鑫,王芳,丁凯阳,等.调节性B细胞在免疫性血小板减少症发病过程中的意义.中国实验血液学杂志,2014;22(2):403-406.
11 Li X,Zhong H,Bao W,et al.Defective regulatory B cell compartment in patients with immune thrombocytopenia.Blood,2012;120(16):3318-3325.
12刘镕,赵琴平,惠芬,等.TGF-β信号传导通路及其生物学功能.中国病原生物学杂志,2014;9(1):77-83.
13 Fang Z,Cai T,Li K,et al.Expression of messenger RNA for transforming growth factor-beta1 and for transforming growth factorbeta receptors in peripheral blood of immune thrombocytopenic purpur.Platelets,2013;24(3):250-252.
14贾瑞萍,赵雪芸.自身免疫性血小板减少性紫癜患者外周血中CD4+CD25+调节性T细胞、sFas和sFasL的表达及临床意义.中国实验血液学杂志,2011;19(5):1264-1267.
15戴兰,王兆钺,张日,等.CD40L在特发性血小板减少性紫癜患者中的表达及其意义.苏州大学学报(医学版),2010;3(6):1224-1225.
16王军,胡玉莲,王西阁,等.特发性血小板减少性紫癜患儿s CD40配体及其m RNA表达水平的变化.中华血液学杂志,2006;13(5):348-349.
17 Gorelik,L,Flavell,R.Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells.Nat Med,2001;7(10):1118-1122.
18 Semple JW,Milev Y,Cosgrave D,et al.Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopennic purpura:relationship to platelet phenotype and antiplatelet T-cells reactivety.Blood,1996;87(10):4245-4254.
19 Morva A,Lemoine S,Achour A,et al.Maturation and function of human dendritic cells are regulated by B lymphocytes.Blood,2012;119(1):106-114.
20 Flores-Borja F,Bosma A,Ng D,et al.CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17differentiation.Sci Transl Med,2013;5(173):173ra23.
21 Mocellin S,Panelli MC,Wang E,et al.The dual role of IL-10.Trends Immunol,2003;24(1):36-43.
2 Gudbrandsdottir S,Ghanima W,Nielsen CH,et al.Effect of thrombopoietin-receptor agonists on circulating cytokine and chemokine levels in patients with primary immune thrombocytopenia(ITP).Platelets,2017;28(5):478-483.
3中华医学会血液学分会血栓与止血学组.成人原发免疫性血小板减少症诊断与治疗中国专家共识(2012年版).中华血液学杂志,2012;33(11):975-977.
4 Wolf SD,Dittel BN,Hardardottir F,et al.Experimental autoimmune encephalomyelitis induction in genetically B cell deficient mice.JExp Med,1996;184(6):2271-2278.
5 Mizoguchi A,Mizoguchi E,Takedatsu H,et al.Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation.Immunity,2002;16(2):219-230.
6 Mizoguchi A,Bhan AK.A case for regulatory B cells.J Immunol,2006;176(2):705-710.
7 Mauri C,Bosma A.Immune regulatory function of B cells.Annu Rev Immunol,2012;30:221-241.
8 Blair PA,Norena LY,Flores-Borja F,et al.CD19+CD24hiCD38hi cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic lupus erythematosus patients.Immunity,2010;32(1):129-140.
9 Noh J,Choi WS,Noh S,et al.Presence of foxp3-expressing CD19+CD5+B cells in human peripheral blood mononuclear cells:human CD19+CD5+foxp3+regulatory B cell(Breg).Immune Netw,2010;10(6):247-249.
10李鑫,王芳,丁凯阳,等.调节性B细胞在免疫性血小板减少症发病过程中的意义.中国实验血液学杂志,2014;22(2):403-406.
11 Li X,Zhong H,Bao W,et al.Defective regulatory B cell compartment in patients with immune thrombocytopenia.Blood,2012;120(16):3318-3325.
12刘镕,赵琴平,惠芬,等.TGF-β信号传导通路及其生物学功能.中国病原生物学杂志,2014;9(1):77-83.
13 Fang Z,Cai T,Li K,et al.Expression of messenger RNA for transforming growth factor-beta1 and for transforming growth factorbeta receptors in peripheral blood of immune thrombocytopenic purpur.Platelets,2013;24(3):250-252.
14贾瑞萍,赵雪芸.自身免疫性血小板减少性紫癜患者外周血中CD4+CD25+调节性T细胞、sFas和sFasL的表达及临床意义.中国实验血液学杂志,2011;19(5):1264-1267.
15戴兰,王兆钺,张日,等.CD40L在特发性血小板减少性紫癜患者中的表达及其意义.苏州大学学报(医学版),2010;3(6):1224-1225.
16王军,胡玉莲,王西阁,等.特发性血小板减少性紫癜患儿s CD40配体及其m RNA表达水平的变化.中华血液学杂志,2006;13(5):348-349.
17 Gorelik,L,Flavell,R.Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells.Nat Med,2001;7(10):1118-1122.
18 Semple JW,Milev Y,Cosgrave D,et al.Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopennic purpura:relationship to platelet phenotype and antiplatelet T-cells reactivety.Blood,1996;87(10):4245-4254.
19 Morva A,Lemoine S,Achour A,et al.Maturation and function of human dendritic cells are regulated by B lymphocytes.Blood,2012;119(1):106-114.
20 Flores-Borja F,Bosma A,Ng D,et al.CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17differentiation.Sci Transl Med,2013;5(173):173ra23.
21 Mocellin S,Panelli MC,Wang E,et al.The dual role of IL-10.Trends Immunol,2003;24(1):36-43.