Mertz Philippe, Boursier Guilaine, Hentgen Véronique, Georgin-Lavialle Sophie
Department of Internal Medicine, Sorbonne University, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, Paris, France; Reference Center for Autoinflammatory Diseases and Inflammatory Amyloidosis, Paris, France; Department of Pediatric Rheumatology, Center Hospitalier de Versailles, Le Chesnay, France; Institut Cochin, Université Paris Cité, INSERM, CNRS, Paris, France.
Reference Center for Autoinflammatory Diseases and Inflammatory Amyloidosis, Paris, France; Service de Génétique Moléculaire et Cytogénomique, Laboratoire de Référence des Maladies Rares et Autoinflammatoires, IRMB, INSERM, CHU Montpellier, Univ Montpellier, Montpellier, France.
J Allergy Clin Immunol Pract. 2025 Mar;13(3):522-532. doi: 10.1016/j.jaip.2024.12.022. Epub 2024 Dec 24.
Autoinflammatory diseases (AIDs) are characterized by dysregulation of innate immunity, leading to systemic inflammation. Familial Mediterranean fever (FMF) is the most common AID, associated with variants in exon 10 of MEFV. This gene codes for pyrin, a key protein in the inflammasome of the same name, involved in the innate immune response. Since the discovery of FMF, many other pathogenic variants of MEFV have been identified. These variants, apart from exon 10, are responsible for a variety of AIDs known as pyrin-associated AIDs or pyrinopathies. Variants in exon 10, 8, 5, and 3 are associated with dominant forms of FMF. Other inflammatory clinical pictures not resembling typical FMF are possible: pyrin-associated autoinflammation with neutrophilic dermatosis is characterized by febrile attacks and severe neutrophilic dermatosis associated with variants in exon 2; pyrin-associated autoinflammation with hypereosinophilia was described among patients displaying severe inflammation and hypereosinophilia-associated variants in exon 2, different from pyrin-associated autoinflammation with neutrophilic dermatosis; and pyrin-associated autoinflammation associated with neuroinflammation manifests with systemic inflammation, serositis, and neuroinflammation associated with variants in exon 9. Somatic forms of FMF have also been described. We present here a review of the literature on the various AIDs associated with pathogenic MEFV variants and propose a practical approach to the genetic diagnosis of MEFV-associated AIDs.
自身炎症性疾病（AIDs）的特征是先天性免疫失调，导致全身炎症。家族性地中海热（FMF）是最常见的AIDs，与MEFV基因第10外显子的变异有关。该基因编码pyrin，它是同名炎性小体中的关键蛋白，参与先天性免疫反应。自FMF被发现以来，已鉴定出许多其他MEFV的致病变异。这些变异除了第10外显子外，还导致了多种被称为pyrin相关的自身炎症性疾病或pyrin病的AIDs。第10、8、5和3外显子的变异与显性形式的FMF相关。其他不类似典型FMF的炎症临床表现也是可能的：与嗜中性皮肤病相关的pyrin相关自身炎症以发热发作和与第2外显子变异相关的严重嗜中性皮肤病为特征；在表现出严重炎症和与第2外显子变异相关的嗜酸性粒细胞增多的患者中描述了与嗜酸性粒细胞增多相关的pyrin相关自身炎症，这与与嗜中性皮肤病相关的pyrin相关自身炎症不同；与神经炎症相关的pyrin相关自身炎症表现为全身炎症、浆膜炎和与第9外显子变异相关的神经炎症。也描述了FMF的体细胞形式。我们在此对与致病性MEFV变异相关的各种AIDs的文献进行综述，并提出一种对MEFV相关AIDs进行基因诊断的实用方法。
