Pediatric Immunology, Hematology and Rheumatology Unit, Hôpital Necker - Enfants Malades, Paris, France.
Division of Rheumatology, Departments of Pediatrics and Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Curr Opin Rheumatol. 2018 Sep;30(5):506-513. doi: 10.1097/BOR.0000000000000532.
This review aims at summarizing the current knowledge of A20 haploinsufficiency and other paediatric inflammatory disorders with mucosal involvement.
A20 haploinsufficiency is a newly described autoinflammatory disease caused by loss-of-function mutations in TNFAIP3 that result in the activation of the nuclear factor (NF)-kB pathway. Patients may present with dominantly inherited, early-onset systemic inflammation and a Behçet-like disease, or a variety of autoinflammatory and autoimmune features. In Behçet disease, recent literature provides insights into genetic susceptibility and emerging treatment options; in addition, the first paediatric classification criteria were published. Recent advances in periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) suggest that the disease has a complex underlying genetic mechanism and in some cases is inherited in an autosomal dominant pattern with reduced penetrance phenotype in many family members. Activation of the pyrin inflammasome through the RoA signalling pathway uncovers an interesting molecular connection between hyperimmunoglobulinemia D syndrome and familial Mediterranean fever. The description of new monogenic types of inflammatory bowel disease (IBD) may provide novel insights into disease pathogenesis. Finally, recent studies highlighted the role of gut microorganisms and dysbiosis in IBD.
Monogenic diseases such as A20 haploinsufficiency may help to advance our understanding of disease pathogenesis and to develop targeted therapies for more common, multifactorial disorders with mucosal inflammation.
本文旨在总结 A20 单倍体不足及其他伴有黏膜累及的儿科炎症性疾病的现有知识。
A20 单倍体不足是一种新描述的自身炎症性疾病，由 TNFAIP3 功能丧失性突变引起，导致核因子（NF）-kB 途径激活。患者可能表现为显性遗传、早发全身炎症和贝切特样疾病，或多种自身炎症和自身免疫特征。在贝切特病中，近期文献提供了对遗传易感性和新兴治疗选择的深入了解；此外，还发布了首个儿科分类标准。周期性发热、口疮性口炎、咽炎和淋巴结炎综合征（PFAPA）的最新进展表明，该疾病具有复杂的潜在遗传机制，在某些情况下以常染色体显性遗传模式遗传，许多家族成员表现为低外显率表型。通过 RoA 信号通路激活 pyrin 炎性小体揭示了高免疫球蛋白 D 综合征和家族性地中海热之间有趣的分子联系。新描述的单基因炎症性肠病（IBD）类型可能为疾病发病机制提供新的见解。最后，最近的研究强调了肠道微生物和失调在 IBD 中的作用。
A20 单倍体不足等单基因疾病可能有助于我们深入了解疾病发病机制，并为伴有黏膜炎症的更常见的多因素疾病开发靶向治疗方法。
