目的:幼年特发性关节炎(JIA)是儿童最常见的风湿性疾病,其发病机制与T细胞活化有关。T细胞活化可以通过抑制性受体(IR)如CTLA-4、PD-1、LAG-3和TIM-3产生的信号平衡。这里,我们确定了IRs在不同JIA亚型发病机制中的作用。
方法:总共,我们纳入了67例少关节JIA,12IgM-RF阴性多关节JIA,17附着炎相关关节炎,11例全身JIA患者和10例健康对照。我们从患者的疾病发作或发作期间收集了血浆(和滑液)样品。我们测量了co-IR(IL-2Rα,4-1BB,CD86,TGF-β1,CTLA-4,PD-L1,PD-1,TIM-3,LAG-3,Galectin-9)通过细胞计数珠阵列试剂盒及其细胞表达(PD-1,CTLA-4,TIM-3,LAG-3)通过流式细胞术。我们比较了不同JIA亚组中不同co-IR的血浆水平和细胞表达。
结果:多关节JIA组与其他三个接受检查的JIA亚组不同,血浆sCTLA-4水平较高(p<0.001),sPD-1(p<0.05),与其他JIA亚组和健康对照相比,s4-1BB(p<0.05)。我们分析了不同JIA亚型的PBMC上不同co-IR的细胞表面表达。类似于血浆水平,poly-JIA亚组CTLA4表达的百分比(p<0.05)和MFI(平均荧光强度)(p<0.01)均较高。
结论:这是研究JIA不同亚型中不同co-IR表达谱的首次报道。多关节JIA患者有不同的共同红外光谱,血浆中的CTLA-4,PD-1和4-1BB比其他JIA亚型多。
OBJECTIVE: Juvenile Idiopathic Arthritis (JIA) is the most common rheumatic disease of childhood; the pathogenesis is associated with T cell activation. T cell activation can be counter-balanced by signals generated by inhibitory receptors (IRs) such as CTLA-4, PD-1, LAG-3, and TIM-3. Here, we identify the role of IRs in the pathogenesis of different JIA subtypes.
METHODS: In total, we included 67 oligoarticular JIA, 12 IgM-RF negative polyarticular JIA, 17 enthesitis related arthritis, 11 systemic JIA patients and 10 healthy controls. We collected plasma (and synovial fluid) samples from the patients either at the onset or during a flare of their disease. We measured the soluble levels of co-IRs (IL-2Rα, 4-1BB, CD86, TGF-β1, CTLA-4, PD-L1, PD-1, TIM-3, LAG- 3, Galectin-9) by cytometric bead array kits and their cellular expression (PD-1, CTLA-4, TIM-3, LAG-3) by flow cytometry. We compared the plasma levels and cellular expressions of different co-IRs within different JIA subgroups.
RESULTS: The polyarticular-JIA group was different from the three other examined JIA subgroups, having higher levels of plasma sCTLA-4(p< 0.001), sPD-1(p< 0.05), and s4-1BB(p< 0.05) when compared with the other JIA subgroups and healthy controls. We analyzed the cellular surface expression of different co-IRs on the PBMCs of different JIA subtypes. Similar to plasma levels, both the percentage(p< 0.05) and the MFI (mean fluorescence intensity) (p< 0.01) of CTLA4 expression were higher in the poly-JIA subgroup.
CONCLUSIONS: This is the first report studying the expression profile of different co-IRs in different subtypes of JIA. Polyarticular JIA patients had a different co-IR profile, having more CTLA-4, PD-1 and 4-1BB in their plasma than the other subtypes of JIA.