Department of Pediatrics, Baylor College of Medicine.
Texas Children's Hospital, Division of Pediatric Immunology, Allergy, and Rheumatology, Houston, Texas, USA.
Curr Opin Pediatr. 2018 Dec;30(6):837-847. doi: 10.1097/MOP.0000000000000696.
Advances in sequencing techniques and systematic cohort-analysis of patients with autoinflammatory phenotypes have enabled a burst in the recognition of new autoinflammatory diseases and contributed to the description of the mechanisms involved in autoinflammation. This review focuses on new genetic and mechanistic discoveries that have broadened the definition of autoinflammatory diseases in the context of the established landscape, providing new therapeutic opportunities and avenues for further discoveries.
Mechanistic insights of inflammatory diseases open opportunities for new targeted therapies. Advances in high-throughput screening of small-molecule inhibitors accelerate the discovery of new and more specific therapeutic options. Recent evidence establishes IL-18 as a driver of macrophage activation, emerging as a new biomarker and therapeutic target. Finally, the identification of escape of nonsense-mediated decay as the genetic mechanism resulting in a monogenic immune-dysregulatory disease, unveils a possibility for future discoveries.
Recent mechanistic findings in autoinflammatory diseases as well as the identification of specific biomarkers and discovery of new diseases, continue to pave the way for ever more specific targeted approaches. These therapies are not only applicable to monogenic autoinflammatory syndromes but also for other diseases in which the same pathways are dysregulated.
测序技术的进步和自身炎症表型患者的系统队列分析，使得人们能够识别新的自身炎症性疾病，并深入了解自身炎症的发病机制。本综述重点介绍了新的遗传和机制发现，这些发现拓宽了既定领域中自身炎症性疾病的定义，为新的治疗机会和进一步发现提供了途径。
炎症性疾病的发病机制研究为新的靶向治疗提供了机会。高通量筛选小分子抑制剂的进展加速了新的更特异治疗选择的发现。最近的证据确立了白细胞介素-18 (IL-18) 作为巨噬细胞活化的驱动因素，它作为一个新的生物标志物和治疗靶点出现。最后，确定无义介导的衰变逃逸是导致单基因免疫调节疾病的遗传机制，为未来的发现开辟了可能性。
自身炎症性疾病的最新发病机制发现，以及特定生物标志物的鉴定和新疾病的发现，继续为更特异的靶向方法铺平道路。这些治疗方法不仅适用于单基因自身炎症性综合征，也适用于其他同样存在通路失调的疾病。
