Patients with autoinflammatory diseases present with noninfectious fever flares and systemic and/or disease-specific organ inflammation. Their excessive proinflammatory cytokine and chemokine responses can be life threatening and lead to organ damage over time. Studying such patients has revealed genetic defects that have helped unravel key innate immune pathways, including excessive IL-1 signaling, constitutive NF-κB activation, and, more recently, chronic type I IFN signaling. Discoveries of monogenic defects that lead to activation of proinflammatory cytokines have inspired the use of anticytokine-directed treatment approaches that have been life changing for many patients and have led to the approval of IL-1-blocking agents for a number of autoinflammatory conditions. In this review, we describe the genetically characterized autoinflammatory diseases, we summarize our understanding of the molecular pathways that drive clinical phenotypes and that continue to inspire the search for novel treatment targets, and we provide a conceptual framework for classification.

中文翻译：

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基因定义的自身炎症性疾病的分子机制：危险信号放大障碍。

患有自身炎性疾病的患者会出现非感染性发热，全身性和/或疾病特异性器官发炎。它们过度的促炎细胞因子和趋化因子反应会威胁生命，并随着时间的推移导致器官损伤。对这类患者的研究表明，遗传缺陷已帮助弄清关键的先天免疫途径，包括过度的IL-1信号传导，组成型NF-κB活化以及最近的慢性I型IFN信号传导。导致促炎细胞因子活化的单基因缺陷的发现启发了抗细胞因子指导的治疗方法的使用，这种治疗方法已改变了许多患者的生活，并导致批准了IL-1阻断剂用于多种自身炎症性疾病。在这篇评论中