Rigante Donato
a Institute of Pediatrics, Periodic Fever Research Center , Fondazione Policlinico Universitario A. Gemelli, Università Cattolica Sacro Cuore , Rome , Italy.
Expert Rev Clin Immunol. 2017 Jun;13(6):571-597. doi: 10.1080/1744666X.2017.1280396. Epub 2017 Feb 1.
Hallmark of autoinflammatory syndromes (AIS) is the periodic recurrence of 'sterile' inflammatory attacks characterized by fever and organ- or tissue-specific inflammation. Basic research projects over the last two decades have boosted our understanding of pathological pathways, mainly involving interleukin (IL)-1 biosynthesis, and also revealed that their dysregulation results from genetically-heterogeneous inborn errors of innate immunity and leads to multiple inflammatory phenotypes. Starting from the evidence of poor response to IL-1 inhibitors of some patients with multi-organ inflammation, further research studies have disclosed a crucial role for nuclear factor (NF)-κB and type I interferon (IFN) in specific AIS. Presently, new genetically-defined AIS have been identified, following the in-depth analysis of molecular pathways which involve either constitutive NF-κB activation or IFN signaling. Areas covered: This review is intended as a spelling booklet to help clinicians approaching patients with AIS in a simple way, using the component of the innate immunity they mainly affect. AIS have been split into 4 groups: IL-1-mediated disorders, NF-κB-mediated disorders, IFN-mediated disorders, and syndromes with still unraveled pathogenetic mechanisms or without any dominating cytokine involved. This classification has mere scholastic purposes and does not reflect the intimate complexity of each disorder discussed herein. Expert commentary: The understanding of dysregulated molecular pathways driving specific phenotypes in most AIS has prompted numerous projects to discover therapies targeting directly cytokine-mediated manifestations in such problematic patients, hopefully aimed to decrease or cancel inflammation and lead to a drastic change in patients' lives. The future has only begun.
自身炎症综合征（AIS）的标志是“无菌性”炎症发作的周期性复发，其特征为发热以及器官或组织特异性炎症。过去二十年的基础研究项目增进了我们对病理途径的理解，主要涉及白细胞介素（IL）-1的生物合成，同时也揭示出其失调是由先天性免疫的基因异质性先天性缺陷导致的，并会引发多种炎症表型。从一些多器官炎症患者对IL-1抑制剂反应不佳的证据出发，进一步的研究揭示了核因子（NF）-κB和I型干扰素（IFN）在特定AIS中的关键作用。目前，在深入分析涉及组成型NF-κB激活或IFN信号传导的分子途径后，已鉴定出新型基因定义的AIS。涵盖领域：本综述旨在作为一本拼写手册，帮助临床医生以简单的方式诊治AIS患者，利用其主要影响的先天性免疫成分。AIS已分为4组：IL-1介导的疾病、NF-κB介导的疾病、IFN介导的疾病，以及发病机制仍未阐明或未涉及任何主导细胞因子的综合征。这种分类仅具有学术目的，并未反映本文所讨论的每种疾病的内在复杂性。专家评论：对大多数AIS中驱动特定表型的失调分子途径的理解促使众多项目去发现针对此类疑难患者直接细胞因子介导表现的疗法，有望旨在减轻或消除炎症并给患者生活带来巨大改变。未来才刚刚开始。
