原发免疫性血小板减少症患者骨髓组织中T细胞和巨噬细胞表达水平及临床意义
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摘要
目的探讨骨髓组织中T细胞和巨噬细胞表达水平在原发免疫性血小板减少症(immune thrombocytopenia,ITP)中的临床意义。方法 26例初诊原发性ITP患者为ITP组,10例同期未侵犯骨髓的淋巴瘤患者为对照组;ITP组患者根据治疗效果再分为有效组14例和无效组12例。采用免疫组织化学法检测各组骨髓组织中T细胞和巨噬细胞的表达水平,分析ITP组骨髓组织中T细胞和巨噬细胞表达水平与外周血血小板计数、性别、年龄的相关性。结果 ITP组T细胞(2 495.16±1 317.20)、M1型巨噬细胞(18 494.42±11 607.42)表达水平均高于对照组(1 589.88±650.72、10 367.40±6 892.06)(P<0.05),M2型巨噬细胞表达水平(3 911.71±940.20)与对照组(3 508.95±2 462.80)比较差异无统计学意义(P>0.05);有效组M2型巨噬细胞表达水平(4 254.27±960.42)高于无效组(3 512.05±771.57)(P<0.05),T细胞(2 582.43±1 402.55)、M1型巨噬细胞表达水平(19 125.06±11 151.70)与无效组(2 393.36±1 263.90、17 758.68±12 575.42)比较差异无统计学意义(P>0.05);ITP组骨髓组织T细胞表达水平与外周血血小板计数呈负相关(r=-0.503,P=0.009),M1、M2型巨噬细胞表达水平与外周血血小板计数无明显相关性(r=-0.107,P=0.602;r=0.222,P=0.276);ITP组T细胞及M1、M2型巨噬细胞表达水平与性别、年龄无相关性(P>0.05)。结论原发性ITP患者骨髓组织中T细胞增加,导致外周血血小板计数减少;促进T细胞及M1型巨噬细胞凋亡,上调M2型巨噬细胞表达,有可能达到治疗原发性ITP并使疾病得到缓解,为原发性ITP治疗提供新靶点。
Objective To investigate the clinical significance of the expression levels of T cells and macrophages in bone marrow in patients with primary immune thrombocytopenia(ITP).Methods Twenty-six patients with initially diagnosed primary ITP were as ITP group,and another 10 lymphoma patients with no bone marrow involvement were as control group.ITP group was redivided into effective group(n=14)and ineffective group(n=12).The expression levels of T cells and macrophages in bone marrow were detected by immunohistochemical method,and the correlations of T cells and macrophages expression with peripheral blood platelet count,gender and age in ITP group were analyzed.Results The expression levels of T cells(2 495.16±1 317.20)and M1 macrophages(18 494.42±11 607.42)in ITP group were significantly higher than those in control group(1 589.88±650.72,10 367.40±6 892.06)(P<0.05),and there was no significant difference in the expression level of M2 macrophages between ITP group(3 911.71±940.20)and control group(3 508.95±2 462.80)(P>0.05).The expression level of M2 macrophages was significantly higher in effective group(4 254.27±960.42)than that in ineffective group(3 512.05±771.57)(P<0.05),and there were no significant differences in the expressions of T cells and M1 macrophages between effective group(2 582.43±1 402.55,19 125.06±11 151.70)and ineffective group(2 393.36±1 263.90,17 758.68±12 575.42)(P>0.05).The expression of T cells was negatively correlated with peripheral blood platelet count in ITP group(r=-0.503,P=0.009),and M1 macrophage and M2 macrophage were not obviously correlated with peripheral blood platelet count(r=-0.107,P=0.602;r=0.222,P=0.276).The expression levels of T cells,M1 macrophages and M2 macrophages in ITP groupwere not correlated with gender and age of the patients(P>0.05).Conclusion The increased T cells in bone marrow leads to a decrease of peripheral blood platelet count in primary ITP patients.Promoting the apoptosis of T cells and M1 macrophages and up-regulating the expression of M2 macrophages might inhibate the development of primary ITP,which provides new targets for the treatment of primary ITP.
Objective To investigate the clinical significance of the expression levels of T cells and macrophages in bone marrow in patients with primary immune thrombocytopenia(ITP).Methods Twenty-six patients with initially diagnosed primary ITP were as ITP group,and another 10 lymphoma patients with no bone marrow involvement were as control group.ITP group was redivided into effective group(n=14)and ineffective group(n=12).The expression levels of T cells and macrophages in bone marrow were detected by immunohistochemical method,and the correlations of T cells and macrophages expression with peripheral blood platelet count,gender and age in ITP group were analyzed.Results The expression levels of T cells(2 495.16±1 317.20)and M1 macrophages(18 494.42±11 607.42)in ITP group were significantly higher than those in control group(1 589.88±650.72,10 367.40±6 892.06)(P<0.05),and there was no significant difference in the expression level of M2 macrophages between ITP group(3 911.71±940.20)and control group(3 508.95±2 462.80)(P>0.05).The expression level of M2 macrophages was significantly higher in effective group(4 254.27±960.42)than that in ineffective group(3 512.05±771.57)(P<0.05),and there were no significant differences in the expressions of T cells and M1 macrophages between effective group(2 582.43±1 402.55,19 125.06±11 151.70)and ineffective group(2 393.36±1 263.90,17 758.68±12 575.42)(P>0.05).The expression of T cells was negatively correlated with peripheral blood platelet count in ITP group(r=-0.503,P=0.009),and M1 macrophage and M2 macrophage were not obviously correlated with peripheral blood platelet count(r=-0.107,P=0.602;r=0.222,P=0.276).The expression levels of T cells,M1 macrophages and M2 macrophages in ITP groupwere not correlated with gender and age of the patients(P>0.05).Conclusion The increased T cells in bone marrow leads to a decrease of peripheral blood platelet count in primary ITP patients.Promoting the apoptosis of T cells and M1 macrophages and up-regulating the expression of M2 macrophages might inhibate the development of primary ITP,which provides new targets for the treatment of primary ITP.
引文
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[6]HOU Y,FENG Q,XU M,et al.High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1in immune thrombocytopenia[J].Blood,2016,127:1587-1597.
[7]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.
[8]孟秋丽,张茵,吴晓邡,等.地塞米松联合利妥昔单抗治疗成人免疫性血小板减少症疗效观察[J].中华实用诊断与治疗杂志,2016,30(9):902-903.
[9]CHEN X,CHEN S,LI C,et al.Skewed T-cell subsets and enhanced macrophages phagocytosis in the spleen of patients with immune thrombocytopenia failing glucocorticoids[J].Int JHematol,2011,94(3):248-254.
[10]BOB O,BORJE R,LENA C,et al.Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4and CX3CR1[J].Blood,2008,112(4):1078-1084.
[11]FENG Q,XU M,YU Y Y,et al.High-dose dexamethasone or all-transretinoic acid restores the balance of macrophages towards M2 in immune thrombocytopenia[J].J Thromb Haemost,2017,15(9):1845-1858.
[12]TOGASAKI E,SHIMIZU N,NAGAO Y,et al.Long-term efficacy of partial splenic embolization for the treatment of steroid-resistant chronic immune thrombocytopenia[J].Ann Hematol,2018,97(4):655-662.
[13]SHAO X,WU B,CHENG L,et al.Distinct alterations of CD68+CD163+M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment[J].J Transl Med,2018,16(1):48-58.
[14]张雷,郝丽荣.巨噬细胞诱导肾间质纤维化机制研究进展[J].中华实用诊断与治疗杂志,2017,31(6):622-624.
[2]郭新红,哈力达·亚森,马艳,等.血小板特异性抗体对特发性血小板减少性紫癜诊断价值的研究[J].中华实用诊断与治疗杂志,2009,23(5):438-440.
[3]HUA F,JI L,ZHAN Y,et al.Aberrant frequency of IL-10-producing B cells and its association with Treg/Th17in adult primary immune thrombocytopenia patients[J].Biomed Res Int,2014:571302.
[4]XU L L,FU H X,ZHANG J M,et al.Impaired function of bone marrow mesenchymal stem cells from immune thrombocytopenia patients in inducing regulatory dendritic cell differentiation through the Notch-1/Jagged-1signaling pathway[J].Stem Cells Dev,2017,26(22):1648-1661.
[5]WYNN T A,CHAWLA A,POLLARD J W.Macrophage biology in development,homeostasis and disease[J].Nature,2013,496(7446):445-455.
[6]HOU Y,FENG Q,XU M,et al.High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1in immune thrombocytopenia[J].Blood,2016,127:1587-1597.
[7]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.
[8]孟秋丽,张茵,吴晓邡,等.地塞米松联合利妥昔单抗治疗成人免疫性血小板减少症疗效观察[J].中华实用诊断与治疗杂志,2016,30(9):902-903.
[9]CHEN X,CHEN S,LI C,et al.Skewed T-cell subsets and enhanced macrophages phagocytosis in the spleen of patients with immune thrombocytopenia failing glucocorticoids[J].Int JHematol,2011,94(3):248-254.
[10]BOB O,BORJE R,LENA C,et al.Recruitment of T cells into bone marrow of ITP patients possibly due to elevated expression of VLA-4and CX3CR1[J].Blood,2008,112(4):1078-1084.
[11]FENG Q,XU M,YU Y Y,et al.High-dose dexamethasone or all-transretinoic acid restores the balance of macrophages towards M2 in immune thrombocytopenia[J].J Thromb Haemost,2017,15(9):1845-1858.
[12]TOGASAKI E,SHIMIZU N,NAGAO Y,et al.Long-term efficacy of partial splenic embolization for the treatment of steroid-resistant chronic immune thrombocytopenia[J].Ann Hematol,2018,97(4):655-662.
[13]SHAO X,WU B,CHENG L,et al.Distinct alterations of CD68+CD163+M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment[J].J Transl Med,2018,16(1):48-58.
[14]张雷,郝丽荣.巨噬细胞诱导肾间质纤维化机制研究进展[J].中华实用诊断与治疗杂志,2017,31(6):622-624.