自噬与全身型幼年特发性关节炎发生的关系及其相关机制的初步研究

Association between autophagy and systemic juvenile idiopathic arthritis and related mechanism: a preliminary study

目的通过研究全身型幼年特发性关节炎(sJIA)患儿外周血淋巴细胞中微管相关蛋白轻链3-Ⅱ(LC3-Ⅱ)、髓样细胞分化因子88(MyD88)及T细胞受体信号抑制因子1(STS-1)的表达,探讨自噬在sJIA发生发展中的作用。方法 26例sJIA患儿及26例健康体检的儿童(对照组)纳入研究。采用Western blot检测外周血淋巴细胞中LC3-Ⅱ、STS-1及MyD88蛋白的表达水平,免疫荧光法检测LC3-Ⅱ在淋巴细胞胞浆中的表达,并采用Pearson相关分析法进行各指标间的相关性分析。结果 sJIA组LC3-Ⅱ、STS-1、MyD88表达均较对照组显著增高,差异有统计学意义(P < 0.05)。sJIA组LC3-Ⅱ表达与MyD88表达呈正相关(r=0.478,P < 0.05);STS-1表达与MyD88表达亦呈正相关(r=0.817,P < 0.01)。结论 sJIA患儿外周血淋巴细胞LC3-Ⅱ高表达,提示sJIA的发生发展与自噬过度表达有关;STS-1可能通过激活某些信号通路诱导自噬的发生;MyD88可能通过Toll样受体信号通路参与自噬的发生。

Objective To study the role of autophagy in the development of systemic juvenile idiopathic arthritis (sJIA) by analyzing the expression of microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ), myeloid differentiation factor 88 (MyD88), and suppressor of T-cell receptor signaling 1 (STS-1) in peripheral blood lymphocytes of children with sJIA.Methods A total of 26 children with sJIA were enrolled as the sJIA group, and 26 healthy children were enrolled as the control group. Western blot was used to measure the protein expression of LC3-Ⅱ, STS-1, and MyD88 in peripheral blood lymphocytes. Immunofluorescence assay was used to measure the expression of LC3-Ⅱ in the cytoplasm of lymphocytes. Pearson correlation analysis was used to assess the correlation between indices.Results Compared with the control group, the sJIA group had significant increases in the expression of LC3-Ⅱ, STS-1, and MyD88 (P < 0.05). In the sJIA group, the expression of LC3-Ⅱ was positively correlated with that of MyD88 (r=0.478, P < 0.05), and the expression of STS-1 was also positively correlated with that of MyD88 (r=0.817, P < 0.05).Conclusions There is high expression of LC3-Ⅱ in peripheral blood lymphocytes of children with sJIA, suggesting that the development of sJIA may be associated with excessive expression of autophagy. STS-1 may induce autophagy by activating some signaling pathways, and MyD88 may participate in autophagy through the Toll-like receptor signaling pathway.