IL-18及其受体在特发性血小板减少性紫癜患者Th1类细胞优势应答中的作用  

The role of interleukin-18 and interleukin-18 receptor in predominant Thl immune response of patients with immune thromboeytopenia

作　　者：王谦[1] 杨晓静[1] 单宁宁[1] 侯明[2] 冀学斌[2] 王春燕[2] 朱效娟[2] 杨蕾[2] 张晓琳[2] 彭军[2] 马道新[2] 石艳[2] 

机构地区：[1]山东大学齐鲁医院检验科,济南250012 [2]山东大学齐鲁医院血液科,济南250012

出　　处：《中华血液学杂志》2009年第10期658-661,共4页Chinese Journal of Hematology

基　　金：国家973资助项目（2006CB503800）;国家自然科学基金（30770922,30600259,30600680,30800489）;国家卫生行业公益性科研项目（200802031）;卫生部临床学科重点项目（2007-2010）;教育部全国优秀博士论文专项基金资助项目（200561）;山东省中青年科学家科研奖励基金（2008BS03009）;山东省自然科学基金（Y2008C121）

摘　　要：目的探讨白细胞介素18（IL-18）及其受体（IL-18R）在特发性血小板减少性紫癜（ITP）患者Th1类细胞因子优势应答中的作用。方法应用逆转录聚合酶链反应（RT-PCR）检测15例活动期和18例缓解期ITP患者外周血单个核细胞（PBMNC）中转录因子T-bet和GATA-3mRNA的表达；应用ELISA法检测血浆中IL-18的变化；应用流式细胞术检测CD3^＋细胞和淋巴细胞表面IL-18R的表达。13名健康志愿者为正常对照。结果ITP活动期患者PBMNC中T-betmRNA表达水平（0．069±0．013）明显高于对照组（0．019±0．010）（P〈0．05），而GATA-3mRNA的表达水平（0．002±0．001）明显低于对照组（0．005±0．002）（P〈0．05）；血浆IL-18和CD3^＋细胞表面IL-18R表达水平较ITP缓解期患者和对照组显著增高。ITP缓解期患者T-bet与GATA-3mRNA表达水平与对照组比较差异均无统计学意义（P值均〉0．05），T-bet／GATA-3比例基本恢复正常，血浆中IL-18和CD3^＋细胞表面IL．18R的表达水平也基本恢复正常。结论ITP活动期患者表现为Th1优势应答，T-bet／GATA-3比例明显失衡，T-bet／GATA-3比例可作为ITP患者Thl类细胞极化的敏感指标；ITP活动期患者IL一18和IL-18R表达上调，可能为ITP患者的治疗提供一个新的治疗靶点。Objective To evaluate the role of interleukin （IL）-18 and IL-18 receptor （IL-18R） in the predominant Thl type cytokine response in patients with immune thrombocytopenia （ITP）. Methods Fifteen patients with active phase ITP, eighteen in remission and thirteen healthy controls were enrolled in this study. T-bet and GATA-3 mRNA levels in peripheral blood mononucleated cells （PBMNC） were measured by reverse transcriptase polymerase chain reaction （RT-PCR） ; the plasma IL-18 level by enzyme linked immu- nosorbent assay （ELISA）, the expression of IL-18R on CD3＋ lymphoeytes and total lymphocytes by flow cy- tometry（FCM）. Results The T-bet mRNA levels in patients with active phase ITP was 3. 572 fold as much as that in the controls （ P 〈 0.05 ） , while the GATA-3 mRNA levels were 0. 378 fold of that in controls （ P 〈 0.05）. The levels of plasma IL-18 and IL-18R on CD3＋ lymphocytes were significantly increased in active phase ITP than in remission phase and controls. There was no difference in ratio of T-bet/GATA-3 between remitted ITP and controls and so was for T-bet mRNA, GATA-3 mRNA, plasma IL-18 and IL-18R on CD3＋ lymphocytes. Conclusion ITP as a disease of Thl-dominant response there is an unbalance between T-bet and GATA-3 in its active phase; IL-18 and IL-18R being upregulated.

关 键 词：紫癜 血小板减少性 特发性 转录因子T-BET 转录因子GATA-3 白细胞介素-18 受体 白细胞介素18 

分 类 号：R686[医药卫生—骨科学]