Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions.
Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions.
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DOI：
10.1038/nrrheum.2011.68
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发表时间：
2011-06-07
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影响因子：
--
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全身型幼年特发性关节炎（sJIA）长期以来被认为在儿童关节炎中是独特的，因其具有独特的临床和流行病学特征，包括与巨噬细胞活化综合征相关。在此，我们总结对sJIA发病机制的研究。疾病的诱因尚不清楚，尽管感染有嫌疑。一旦发病，sJIA似乎是由先天性促炎细胞因子驱动。内源性Toll样受体配体，包括S100蛋白，可能与细胞因子协同作用使炎症持续。这些及其他发现支持sJIA是一种自身炎症性疾病这一假说。事实上，白细胞介素 - 1被认为是一种关键的细胞因子，但过量白细胞介素 - 1活性的来源仍不清楚，且白细胞介素 - 1在慢性关节炎中的作用也不太明确。另一种假说认为噬血细胞性淋巴组织细胞增生症的一种形式是sJIA的基础，在疾病谱中其表现程度不同。或者，伴有巨噬细胞活化综合征的sJIA可能是一种基因上不同的亚型。还有一种假说提出免疫激活的下调不充分是sJIA的核心，支持这一说法的证据包括单核细胞和巨噬细胞的“替代性激活”以及白细胞介素 - 10和调节性T细胞可能存在的缺陷。一些改变的免疫表型在临床缓解期仍然存在，这表明该阶段可能代表代偿性炎症。尽管取得了很大进展，但仍有许多问题存在，为未来的研究提供了沃土。
Systemic juvenile idiopathic arthritis (sJIA) has long been recognized as unique among childhood arthritides, because of its distinctive clinical and epidemiological features, including an association with macrophage activation syndrome. Here, we summarize research into sJIA pathogenesis. The triggers of disease are unknown, although infections are suspects. Once initiated, sJIA seems to be driven by innate proinflammatory cytokines. Endogenous Toll-like receptor ligands, including S100 proteins, probably synergize with cytokines to perpetuate inflammation. These and other findings support the hypothesis that sJIA is an autoinflammatory condition. Indeed, IL-1 is implicated as a pivotal cytokine, but the source of excess IL-1 activity remains obscure and the role of IL-1 in chronic arthritis is less clear. Another hypothesis is that a form of hemophagocytic lymphohistiocytosis underlies sJIA, with varying degrees of its expression across the spectrum of disease. Alternatively, sJIA with MAS might be a genetically distinct subtype. Yet another hypothesis proposes that inadequate downregulation of immune activation is central to sJIA, supporting evidence for which includes ‘alternative activation’ of monocyte and macrophages and possible deficiencies in IL-10 and T regulatory cells. Some altered immune phenotypes persist during clinically inactive disease, which suggests that this stage might represent compensated inflammation. Despite much progress being made, many questions remain, providing fertile ground for future research.
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DOI：
10.1073/pnas.212519099
发表时间：
2002-10-15
影响因子：
11.1
作者：
Bufler, P;Azam, T;Kim, SH
通讯作者：
Kim, SH
影响因子：
--
作者：
de Jager, Wilco;Vastert, Sebastiaan J.;Prakken, Berent J.
通讯作者：
Prakken, Berent J.
影响因子：
--
作者：
Fall, Ndate;Barnes, Michael;Grom, Alexei A.
通讯作者：
Grom, Alexei A.
影响因子：
--
作者：
De Benedetti, F;Meazza, C;Martini, A
通讯作者：
Martini, A
影响因子：
30.8
作者：
Coffey, AJ;Brooksbank, RA;Bentley, DR
通讯作者：
Bentley, DR