Leeds Institute of Rheumatic and Musculoskeletal Medicine, St James's University Hospital, Leeds, UK.
National Institute for Health Research-Leeds Biomedical Research Centre, Chapel Allerton Hospital, Leeds, UK.
Nat Rev Rheumatol. 2020 Apr;16(4):222-237. doi: 10.1038/s41584-020-0377-5. Epub 2020 Feb 27.
Autoinflammation as a distinct disease category was first reported in 1999 as a group of monogenic disorders characterized by recurrent episodes of systemic and organ-specific inflammation, known as periodic fever syndromes. Since this original description, the focus has shifted considerably to the inclusion of complex multifactorial conditions with an autoinflammatory basis. Furthermore, the boundaries of what are considered to be autoinflammatory disorders are constantly evolving and currently encompass elements of immunodeficiency and autoimmunity. Notable developments in the intervening 20 years include substantial progress in understanding how the different inflammasomes are activated, how infection is sensed by the innate immune system and how intracellular signalling systems are consequently activated and integrated with many different cellular functions in the autoinflammatory process. With these developments, the field of autoinflammation is moving from a gene-centric view of innate immune-mediated disease towards a systems-based concept, which describes how various convergent pathways, including pyrin and the actin cytoskeleton, protein misfolding and cellular stress, NF-κB dysregulation and interferon activation, contribute to the autoinflammatory process. The development and adoption of a systems-based concept of systemic autoinflammatory diseases is anticipated to have implications for the development of treatments that target specific components of the innate immune system.
自身炎症作为一个独特的疾病类别，于 1999 年首次被报道，它是一组由反复发作的全身性和器官特异性炎症组成的单基因疾病，称为周期性发热综合征。自最初的描述以来，人们的关注点已经大大转移到包括具有自身炎症基础的复杂多因素疾病。此外，被认为是自身炎症性疾病的范围也在不断变化，目前包括免疫缺陷和自身免疫的元素。在这 20 年的时间里，值得注意的发展包括在理解不同的炎症小体如何被激活、先天免疫系统如何感知感染以及细胞内信号系统如何随后被激活以及与自身炎症过程中的许多不同细胞功能整合方面取得了实质性进展。随着这些发展，自身炎症领域正在从先天免疫介导疾病的基因中心观点向系统为基础的概念转变，该概念描述了包括 pyrin 和肌动蛋白细胞骨架、蛋白质错误折叠和细胞应激、NF-κB 失调和干扰素激活在内的各种汇聚途径如何导致自身炎症过程。预计系统为基础的全身性自身炎症性疾病概念的发展和采用将对针对先天免疫系统特定成分的治疗方法的发展产生影响。
