Department of Immunology & Histocompatibility, School of Medicine, University of Thessaly, Larissa, Greece.
Dipartimento di Scienze Biomediche e Cliniche Luigi Sacco, Universita Degli Studi di Milano, IRCCS ICS Maugeri Milano via Camaldoli, Italy.
J Autoimmun. 2019 Nov;104:102312. doi: 10.1016/j.jaut.2019.102312. Epub 2019 Aug 9.
Evidence accumulated over the last two decades indicates that recurrent angioedema without wheals constitutes a diverse family of disorders with a much higher complexity than was previously regarded. Indicatively, during the last two years, novel variants of three genes other than SERPING1 and F12 have been identified in association with hereditary angioedema. Most interestingly, functional studies of at least one of these variants (the variant c.807G > T of ANGPT1 gene) imply the existence of a new disease endotype in which the altered bradykinin metabolism and function does not play a central role. Therefore, using conventional approaches, it seems that the complexity of this disease cannot be sufficiently elucidated and any attempt to interrelate its many diverse aspects seems unrealistic. Similar to other rare and chronic diseases, a Precision Medicine approach, discovering the right target and giving "the right drug, for the right patient, at the right time, every time" seems the optimal future practice. Herein, we review recent data challenging and dictating the need for a switch of angioedema research into high-throughput approaches and we present the expected advantages for better understanding of the disease and patients management.
过去二十年积累的证据表明，无风团反复性血管性水肿是一种具有高度复杂性的多种疾病家族，其复杂性远远超出了以前的认识。有代表性的是，在过去两年中，除了 SERPING1 和 F12 之外，另外三个基因的新型变体已被确定与遗传性血管性水肿有关。最有趣的是，这些变体之一（ANGPT1 基因的 c.807G>T 变体）的功能研究表明，存在一种新的疾病表型，其中改变的缓激肽代谢和功能不再起核心作用。因此，使用传统方法似乎无法充分阐明这种疾病的复杂性，而且试图将其众多不同方面联系起来似乎不切实际。与其他罕见和慢性疾病一样，精准医学方法似乎是未来的最佳实践，即发现正确的靶点，并“在每次需要时，为每个合适的患者，提供合适的药物”。在此，我们回顾了最近的数据，这些数据挑战并要求将血管性水肿研究转向高通量方法，并展示了更好地理解疾病和患者管理的预期优势。
