可诱导共刺激因子在类风湿关节炎外周血和关节滑液细胞的表达  

Expression and role of the inducible costimulator (ICOS) in patients with rheumatoid arthritis

作　　者：蔡青[1] 张军[2] 刘彧[1] 张兰玲[1] 韩星海[1] 沈茜[2] 

机构地区：[1]第二军医大学附属长海医院风湿免疫科,上海200433 [2]第二军医大学附属长海医院实验诊断科,上海200433

出　　处：《中华风湿病学杂志》2006年第11期650-653,共4页Chinese Journal of Rheumatology

基　　金：国家"863"高技术研究发展计划基金资助项目(2002AA214091);上海市科委自然科学基金资助项目(03ZR14026)

摘　　要：目的探讨可诱导共刺激因子(ICOS)在类风湿关节炎(RA)外周血和关节滑液的表达和作用。方法选择RA患者45例,年龄18-71岁,平均(48±16)岁,病程0．5～17年,平均(6±7)年,男性9例,女性36例(80％)。取新鲜抗凝外周血单个核细胞(PBMC)行ICOS、CD45RO和CD45RA在CD4^+、CD8^+ T淋巴细胞亚群的双色和或三色表达百分比。其中15例同时行关节液单个核细胞(SFMC)进行相同的检查。与RA患者年龄和性别匹配的正常体检者56名作为对照。结果①CD4^+ICOS^+/CD4^+在RA的PBMC较正常对照组明显下降(P=0．0175),在RA的SFMC非常显著升高(与RA的PBMC比较,P=0．0020)；②CD8^+ICOS^+/CD8^+在RA患者的PBMC较正常对照组明显下降(P=0．0193),在RA的SFMC升高但差异无统计学意义(与PBMC比较,P=0．0933)；③CD45RO^+ICOS^+/CD4^+在RA的SFMC较PBMC显著升高(P= 0．0330),CD45RO^+ICOS^+/CD8^+在SFMC较PBMC也明显升高(P=0．0588),可能扩大例数后能达到有统计学意义的显著升高；④B淋巴细胞上的CD19^+ICSOL^+/CD19^+在RA的PBMC升高(与对照相比差异无统计学意义),而在SFMC则降低(与PBMC相比,P=0．0123)。⑤将RA患者按病情分为活动与非活动,非活动性RA外周血细胞CD19B细胞表达的ICOSL(ICOS配体)百分比较活动性RA非常显著地升高(P=0．0016)。其他各组T细胞表达的ICOS没有显著性变化。结论RA活化的T淋巴细胞主要集中于关节液中,故无论是CD4^+,还是CD8^+细胞,表达ICOS及其与CD45RO记忆细胞三色表达均较血液有非常显著地升高,而且是非常敏感的指标。而关节液B淋巴细胞表面的ICOSL较血液中下降,尤其是活动组较非活动组非常显著地下降。说明RA关节局部发生了由ICOS介导的免疫反应,并可能参与了关节的破坏活动。Objective To assessed the expression of inducible costimulator （ICOS） on peripheral blood and joint fluid CD4,CD8, CD45RO T cells and B cells in rheumatoid arthritis （RA）. Methods Expression of ICOS and ICOS/CD45RO on peripheral blood and joint fluid CD4^＋CD8^＋T cells and ICOS ligand （ICOSL） on CD19 B cells from RA patients and healthy volunteers were determind by three-color flow cytometry. Comparision with active and inactive RA, initial and relapsed RA had been done. Results Joint fluid CD4 and CD8 T cells expressing ICOS, ICOS/CD45RO were significantly increased than peripheral blood in RA patients and healthy subjects. Joint fluid B cells expressing ICOSL were significantly reduced than peripheral blood in RA patients. Meanwhile, peripheral blood B cells expressing ICOSL were significantly reduced in active RA than inactive RA patients. Conclusion Hyperexpression of ICOS and ICOS/CD45RO on joint fluid CD4 and CD8 T cells and lowexpression of ICOSL in B cells from RA patients, expecially in active RA may contribute to the local immunopathological roles and joint destructions in the pathogenesis of RA.

关 键 词：关节炎 类风湿 流式细胞术 可诱导共刺激因子 

分 类 号：R593.22[医药卫生—内科学]