CHRU Montpellier, UM1, INSERMU844, UMAI, laboratoire de génétique, Hopital A de Villeneuve, 34295, Montpellier Cedex 15, France.
J Med Genet. 2013 Jun;50(6):349-59. doi: 10.1136/jmedgenet-2013-101577. Epub 2013 Mar 27.
Over 15 years have passed since the discovery of the first autoinflammatory gene, MEFV, responsible for familial Mediterranean fever. The identification of another gene, TNFRSF1A, in 1999 led to the concept of autoinflammation which characterises rheumatological conditions triggered by a defective innate immunity. Substantive progress has been made since then with the identification of 18 autoinflammatory genes accounting for up to 24 disease entities showing overlapping symptoms. The accumulation of studies reporting patients with missing or excess mutations as compared with expected numbers favours the hypothesis that these diseases are distributed along a continuum ranging from monogenic to multifactorial conditions, rather than featuring only classical modes of inheritance. Moreover, the probable interactions of environmental and epigenetic factors further obscure our understanding of the mechanisms underlying the phenotypic expression of patients. This review explores the history of autoinflammatory gene discovery, discusses the nosological disparities stemming from the clinical versus pathophysiological definition of autoinflammatory diseases and summarises various inheritance patterns. This review calls for a consistent disease nomenclature and presents a reconciling hypothesis which places different sequence variants within the autoinflammatory disease continuum. Integrating these new concepts should help to facilitate communication between health professionals and promote personalised patient care.
自发现首个自身炎症基因 MEFV （家族性地中海热）以来，已经过去了 15 年。1999 年 TNFRSF1A 基因的鉴定导致了自身炎症的概念的产生，其特征是先天免疫缺陷引发的风湿性疾病。此后，随着 18 个自身炎症基因的鉴定，多达 24 种疾病实体的重叠症状，取得了实质性的进展。越来越多的研究报告显示，与预期数量相比，患者缺失或过度突变，这支持了这样一种假设，即这些疾病沿着从单基因到多因素条件的连续体分布，而不仅仅是具有经典的遗传模式。此外，环境和表观遗传因素的可能相互作用进一步模糊了我们对患者表型表达背后机制的理解。这篇综述探讨了自身炎症基因发现的历史，讨论了从临床与病理生理学定义自身炎症性疾病的分类学差异，并总结了各种遗传模式。这篇综述呼吁使用一致的疾病命名法，并提出了一个协调的假说，将不同的序列变体置于自身炎症疾病连续体中。整合这些新概念应该有助于促进卫生专业人员之间的沟通，并促进个性化的患者护理。
