Department of Rheumatology, Fukushima Medical University School of Medicine, Japan.
Intern Med. 2023;62(1):43-50. doi: 10.2169/internalmedicine.09279-21. Epub 2023 Jan 1.
Autoinflammatory diseases are systemic disorders caused by genetic or acquired abnormalities in certain signaling pathways of the innate immune system. Dysregulated activation of the inflammasome, i.e. molecular platforms responsible for the activation of caspase-1 and production of interleukin-1β, causes autoinflammation. Familial Mediterranean fever (FMF), the most common genetic autoinflammatory disease, is characterized by a periodic fever and serositis. The complex and heterogeneous genetic background of Japanese FMF patients, accompanied by potential overlap with other rheumatic diseases, suggests crosstalk between genetic and environmental factors. Recently, FMF has been recognized as being part of a spectrum of autoinflammatory syndromes named pyrin-associated autoinflammatory diseases. The discovery of a new monogenic autoinflammatory disease, A20 haploinsufficiency, may provide novel insights into early-onset Behçet's-like diseases. In contrast, adult-onset Still's disease and Schnitzler's syndrome are acquired autoinflammatory diseases without a monogenic abnormality. Although the concept of autoinflammatory diseases originally applied to monogenic hereditary recurrent fevers, it has been expanded to include non-genetic complex autoinflammatory diseases. Information concerning monogenic autoinflammatory diseases may prove useful for elucidating the molecular mechanisms underlying non-genetic autoinflammatory diseases.
自身炎症性疾病是由固有免疫系统某些信号通路的遗传或获得性异常引起的全身性疾病。炎症小体的失调激活，即负责激活 caspase-1 和产生白细胞介素-1β的分子平台，导致自身炎症。家族性地中海热（FMF）是最常见的遗传性自身炎症性疾病，其特征是周期性发热和浆膜炎。日本 FMF 患者复杂和异质的遗传背景，伴随着与其他风湿性疾病的潜在重叠，表明遗传和环境因素之间存在相互作用。最近，FMF 被认为是一种名为 pyrin 相关自身炎症性疾病的自身炎症综合征谱的一部分。新发现的单基因自身炎症性疾病 A20 单倍不足，可能为早发性 Behçet 样疾病提供新的见解。相比之下，成人Still 病和 Schnitzler 综合征是获得性自身炎症性疾病，没有单基因异常。尽管自身炎症性疾病的概念最初适用于单基因遗传性复发性发热，但已扩展到包括非遗传复杂自身炎症性疾病。关于单基因自身炎症性疾病的信息可能有助于阐明非遗传自身炎症性疾病的分子机制。
