Translational Autoinflammatory Disease Section, MSC 1560, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Curr Opin Rheumatol. 2010 Sep;22(5):567-78. doi: 10.1097/BOR.0b013e32833ceff4.
The genetic and clinical characterizations of monogenic autoinflammatory syndromes have led to ground breaking insights into the regulation of inflammatory responses to endogenous and exogenous inducers or triggers of inflammation and continue to uncover key inflammatory pathways of the innate immune system. This article summarizes recent progress in the clinical aspects and understanding of the pathogenesis of this growing spectrum of diseases.
The understanding of the spectrum of organ manifestations in autoinflammation was expanded by the discovery of two novel monogenic diseases both caused by the absence of an anti-inflammatory signal and added evidence that increased IL-1 signaling can cause aseptic osteolytic bone lesions and that the absence of IL-10 signaling causes inflammatory enterocolitis in neonates. New knock in animal models for TNF-receptor-associated periodic syndrome, and familial Mediterranean fever and cryopyrin-associated periodic syndromes allow insights into the complexity of the dysregulated immune pathways. Exploring 'triggers' of the NLRP3 inflammasome spurred studies of tissue inflammation in diseases including gout and those that previously have not been considered inflammatory in nature such as diabetes, fibrosing lung disease and possibly coronary artery disease.
The genetic characterization of a growing number of monogenic autoinflammatory diseases has provided important insights into the phenotypic expression of single gene disorders and the complexity of the dysregulated inflammatory pathways leading to clinical disease. Knowledge obtained from these disorders is pertinent to a number of common disorders and provides new targets for drug development.
单基因自身炎症性疾病的遗传学和临床特征，使人们对炎症反应的调控有了突破性的认识，包括内源性和外源性炎症诱导物或触发物，并且不断揭示先天免疫系统的关键炎症途径。本文总结了该疾病谱在临床方面和发病机制方面的最新进展。
通过发现两种新的单基因疾病，即缺乏抗炎信号的疾病，扩大了对自身炎症疾病器官表现谱的认识，并进一步证明了增加 IL-1 信号可以导致无菌性溶骨性骨病变，而缺乏 IL-10 信号会导致新生儿炎症性肠炎。新的 TNF 受体相关周期性综合征、家族性地中海热和 Cryopyrin 相关周期性综合征的基因敲入动物模型使人们能够深入了解失调免疫途径的复杂性。探索 NLRP3 炎性体的“触发因素”促使人们研究痛风等疾病以及以前被认为非炎症性疾病（如糖尿病、纤维性肺病，可能还有冠状动脉疾病）中的组织炎症。
越来越多的单基因自身炎症性疾病的遗传学特征为单基因疾病的表型表达和导致临床疾病的失调炎症途径的复杂性提供了重要的见解。从这些疾病中获得的知识与许多常见疾病有关，并为药物开发提供了新的靶点。
