Division of Rheumatology, Cincinnati Children's Hospital Medical Center.
Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Rheumatology (Oxford). 2022 Mar 2;61(3):926-935. doi: 10.1093/rheumatology/keab673.
Systemic JIA (SJIA) is distinguished from other forms of JIA by the prevalence of the severe, life-threatening complications macrophage activation syndrome (SJIA-MAS) and lung disease (SJIA-LD). Alternative therapeutics are urgently needed, as disease pathogenesis diverges from what is observed in SJIA, and currently available biologics are insufficient. SJIA-MAS, defined by a cytokine storm and dysregulated proliferation of T-lymphocytes, and SJIA-LD which presents with lymphocytic interstitial inflammation and pulmonary alveolar proteinosis, are both thought to be driven by IFNs, in particular the type II IFN-γ. Involvement of IFNs and a possible crosstalk of type I IFNs with existing biologics indicate a distinct role for the JAK-STAT signalling pathway in the pathogenesis of SJIA-MAS and SJIA-LD. Here, we review this role of JAK-STATs and IFNs in SJIA complications and discuss how new insights of ongoing research are shaping future therapeutic advances in the form of JAK inhibitors and antibodies targeting IFNs.
全身型幼年特发性关节炎（SJIA）以严重的、危及生命的并发症巨噬细胞活化综合征（SJIA-MAS）和肺部疾病（SJIA-LD）为特征，与其他类型的幼年特发性关节炎（JIA）不同。由于疾病发病机制与 SJIA 不同，目前可用的生物制剂也不足，因此迫切需要替代疗法。SJIA-MAS 由细胞因子风暴和 T 淋巴细胞失调性增殖定义，SJIA-LD 表现为淋巴细胞间质性炎症和肺泡蛋白沉积症，两者均被认为是由 IFNs 驱动的，特别是 II 型 IFN-γ。IFNs 的参与以及 I 型 IFNs 与现有生物制剂的可能串扰表明，JAK-STAT 信号通路在 SJIA-MAS 和 SJIA-LD 的发病机制中具有独特的作用。在这里，我们回顾了 JAK-STAT 和 IFNs 在 SJIA 并发症中的作用，并讨论了正在进行的研究的新见解如何以 JAK 抑制剂和针对 IFNs 的抗体的形式为未来的治疗进展提供新的思路。
