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

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。

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

Objective To assessed the expression of inducible costimulator(ICOS)on peripheral blood and joint fluid CD4,CDS,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.Compar- ision 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.