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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 investigate the expression and effect of inducible co-stimulatory factor (ICOS) on peripheral blood and synovial fluid in rheumatoid arthritis (RA). Methods A total of 45 RA patients (aged 18-71 years, mean age 48 ± 16 years) with a duration of 0.5 to 17 years (average 6 ± 7 years) were enrolled in this study. There were 9 males and 36 females (80%). Take fresh anticoagulant peripheral blood mononuclear cells (PBMC) ICOS, CD45RO and CD45RA in CD4 ~ +, CD8 ~ T lymphocyte subsets two-color and or three-color expression percentage. 15 of them simultaneously performed synovial fluid mononuclear cells (SFMC) for the same examination. Fifty-six healthy subjects who matched the age and sex of RA patients served as controls. Results ① The PBMC of CD4 ~ + ICOS ~ + / CD4 ~ + in RA decreased significantly (P = 0.0175) and the level of SFMC in RA increased significantly (P = 0.0020 compared with PBMC of RA) ; ②CD8 ~ + ICOS ~ + / CD8 ~ + in RA patients decreased significantly (P = 0.0193) compared with the normal control group, but there was no significant difference in SFMC in RA (P = 0 (P = 0.0330). The levels of CD45RO ~ + ICOS ~ + / CD8 ~ + in SFMC were significantly higher than those in PBMC (P <0.01) P = 0.0588), and it is possible to reach a statistically significant increase after the number of cases can be enlarged. (4) CD19 ~ + ICSOL ~ + / CD19 ~ + on B lymphocytes increased in PBMC of RA (compared with the control Not statistically significant), but decreased in SFMC (P = 0.0123 compared to PBMC). (5) The percentage of ICOSL (ICOS ligand) expressed by CD19B cells in active and inactive RA patients was significantly higher than that in active RA (P = 0.0016). ICOS expression of other groups of T cells did not change significantly. Conclusion RA-activated T lymphocytes are mainly concentrated in synovial fluid. Therefore, both the expression of ICOS and CD45RO memory cells both in CD4 ~ + and CD8 ~ + cells are significantly higher than those in blood Very sensitive indicator. The synovial fluid B lymphocytes on the surface of ICOSL decreased compared with the blood, especially active than non-active group decreased significantly. It shows that the ICR-mediated immune response occurs locally in RA joints and may be involved in the destruction of joints.