Table_1_Emerging Place of JAK Inhibitors in the Treatment of Inborn Errors of Immunity.docx

Among inborn errors of immunity (IEIs), some conditions are characterized by inflammation and autoimmunity at the front line and are particularly challenging to treat. Monogenic diseases associated with gain-of-function mutations in genes critical for cytokine signaling through the JAK-STAT pathway belong to this group. These conditions represent good candidates for treatment with JAK inhibitors. Type I interferonopathies, a group of recently identified monogenic auto-inflammatory diseases characterized by excessive secretion of type I IFN, are also good candidates with growing experiences reported in the literature. However, many questions remain regarding the choice of the drug, the dose (in particular in children), the efficacy on the various manifestations, the monitoring of the treatment, and the management of potent side effects in particular in patients with infectious susceptibility. This review will summarize the current experiences reported and will highlight the unmet needs.

在原发性免疫缺陷病（inborn errors of immunity，IEIs）这一类疾病中，部分以炎症与自身免疫为核心临床表现，治疗颇具挑战。其中，若单基因疾病的功能获得性突变发生在对JAK-STAT信号通路（JAK-STAT pathway）至关重要的细胞因子信号传导相关基因中，则该疾病即属于此类范畴。这类疾病是JAK抑制剂（JAK inhibitors）治疗的理想候选对象。近期新发现的单基因自身炎症性疾病——I型干扰素病（Type I interferonopathies），以I型干扰素（type I IFN）过度分泌为典型特征，同样适宜采用JAK抑制剂治疗，相关临床应用经验正不断见诸文献报道。然而，当前仍存在诸多亟待解决的问题，包括药物选择、给药剂量（尤其针对儿童患者）、对多种临床表型的疗效、治疗监测方案，以及如何管理潜在的严重不良反应，尤其是在存在感染易感性的患者群体中。本综述将总结目前已报道的临床应用经验，并着重阐明当前尚未被满足的临床需求。