白介素1等固有免疫相关因子在全身型幼年型特发性关节炎巨噬细胞活化综合征中的作用相关研究

Systemic-onset juvenile idiopathic arthritis (soJIA) is an subset of juvenile idiopathic arthritis. SoJIA is considered to be caused by the activation of innate immunity. Cytokines of the innate immunity, such as interleukin-1 (IL-1) and interleukin-6 (IL-6) etc, are involved in the pathogenesis of soJIA. Macrophage activation syndrome (MAS) is a severe complication of soJIA. MAS was supposed to happen in approximately 5-8% of soJIA patients, but the occurrence of occult MAS is supposed to be close to 30-40% recently. Although the mortality of MAS is relatively high, the mechanism of MAS is still unclear. Recent study illustrate that MAS may associated with interferon-gamma (IFN-gamma). It is obscure that IFN-gamma is associated with MAS in soJIA patients, which is supposed to be closely related to innate immunity. Is there any cytokines of innate immunity may also play an important role in the pathogenesis of MAS/soJIA? We are going to detect the level of cytokines like IL-1 of innate immunity and associated pathways in this study. Further, through functional block assay of cytokines like IL-1 to make clear whether cytokines likes IL-1 is essential for the pathogenesis of MAS in soJIA patients.

全身型幼年型特发性关节炎（soJIA）是儿童特发性关节炎中的一种亚型，近年来认为由于固有免疫的过度活化而导致的，IL-1、IL-6等固有免疫相关细胞因子均积极参与到疾病的发病过程中。巨噬细胞活化综合征(MAS)是soJIA的一种严重并发症，早期认为其发生率为5-8%，近期研究显示隐匿性MAS可高达30-40%，然而目前对于其确切的发病机制尚不明了，可能与干扰素gamma有关。然而为什么soJIA在合并MAS时却可能与干扰素gamma密切相关是非常令人费解的，或许IL-1等固有免疫相关细胞因子/信号通路对于soJIA/MAS的发生亦起着重要的作用。本研究拟通过对soJIA/MAS患者进行IL-1等细胞因子以及相关基因的分析，了解其表达特征，并通过在soJIA/MAS小鼠模型中对IL-1等细胞因子进行功能阻断实验，从而明确IL-1等细胞因子是否在soJIA/MAS的发病机制中亦起着重要作用。

巨噬细胞活化综合征（MAS）是全身型幼年型特发性关节炎（soJIA）患儿中具有潜在危及生命的并发症。其发病机制不明，而参与到soJIA发病中的重要细胞因子IL-1、IL-6是否也是导致MAS发生的重要因子尚不明了。通过本研究我们能了解IL-1及IL-6是否是MAS/soJIA的重要发病因子，这将有助于MAS/soJIA的早期诊断、及时治疗。本研究通过对Toll样受体9 (TLR9) 刺激物诱导的MAS 小鼠模型的研究，本研究发现IL-1、IL-6的拮抗剂在TLR9刺激物诱导的MAS小鼠模型中并不能有效阻止MAS的发生，提示IL-1、IL-6可能并不是soJIA/MAS发生的重要参与因子，这提示我们soJIA患儿在发生MAS时其内在的免疫状态发生了改变，可能有新的免疫活性因子参与到MAS的发生中，这对于我们未来开展新的MAS/soJIA的发病机制研究有一定意义。