TIPE2在类风湿关节炎发病中的表达及其意义

The expression of TIPE2 and its role in the pathogenesis of rheumatoid arthritis

目的探讨TIPE2（tumor necrosis factor—α induced protein 8 like 2）在牛Ⅱ型胶原诱导的CIA模型小鼠脾脏及类风湿关节炎（rheumatoid arthritis，RA）患者的外周血淋巴细胞中的表达及其意义。方法使用牛Ⅱ型胶原免疫DBA-1／j小鼠，建立CIA小鼠模型；半定量RT-PCR法检测CIA小鼠脾脏中TIPE2基因的表达变化，荧光定量RT-PCR检测患者和健康对照者新鲜分离的淋巴细胞中TIPE2基因的表达差异；Westernblot检测CIA小鼠脾脏及患者淋巴细胞中TIPE2蛋白表达差异。并研究TIPE2与类风湿关节炎患者病情活动程度的关系。结果CIA小鼠的脾脏细胞中和患者外周血淋巴细胞中TIPE2在mRNA和蛋白水平表达增强，此外类风湿患者在活动期TIPE2表达更高，差异有统计学意义。类风湿关节炎患者的TIPE2表达水平和DAS28评分成明显正相关（P〈0．001）。结论TIPE2参与了类风湿关节炎的发病过程，TIPE2可能是评价类风湿关节炎患者病情严重程度的标志物。

Objective To investigate the expression of TIPE2 in splenic lymphocytes derived from the mouse model of cattle collagen II -induced rheumatoid arthritis （CIA） and from peripheral blood of patients with rheumatoid arthritis （RA） for its role in the pathogenesis of RA. Methods The CIA mouse model was established by immunization of DBA-1/J mice with cattle collagen II. Peripheral blood lymphocytes were collected from RA patients and healthy donors. The TIPE2 mRNA and protein expression in splenocytes of CIA and control mice were measured by semi-quantitative RT-PCR and Western blot, respectively. In addition, fluorescence quantitative RT-PCR and Western blot were used to determine the TIPE2 mRNA and protein expression in peripheral blood lymphocytes derived from patients with RA and healthy do- nors. Results Both mRNA and protein expression of TIPE2 were higher in splenocytes of CIA mice and lymphocytes of peripheral blood from RA patients compared with corresponding controls. Furthermore, the mRNA and protein expression of TIPE2 increased significantly in patients with active RA. TIPE2 expression were positively correlated with DAS28 scores （P〈 0. 001 ）. Conclusion Our results suggest that TIPE2 plays a role in the RA pathogenesis. The level of TIPE2 may also indicate the severity of rheumatoid arthritis.