沙特阿拉伯国王大学医学院Abdullah A. Alangari研究小组取得一项新突破。他们研究了JAK抑制剂治疗遗传性USP18缺乏症的效果。这一研究成果发表在2020年1月16日出版的国际学术期刊《新英格兰医学杂志》上。

泛素特异性肽酶18（USP18）缺乏是一种严重的I型干扰素病。USP18通过阻断Janus相关激酶1（JAK1）访问I型干扰素受体来下调I型干扰素信号传导。USP18的缺失导致干扰素介导的炎症，在围产期是致命的。

研究组描述了一例患脑积水、坏死性蜂窝织炎、全身炎症和呼吸衰竭的新生儿。外显子组测序鉴定出USP18一个重要剪接位点的纯合子突变。编码蛋白已表达，但是没有负调控能力。用ruxolitinib治疗后迅速康复，且未复发。

附：英文原文

Title: JAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency

Author: Fahad Alsohime, M.D.,, Marta Martin-Fernandez, Ph.D.,, Mohamad-Hani Temsah, M.D.,, Majed Alabdulhafid, M.D.,, Tom Le Voyer, M.S.,, Malak Alghamdi, M.D.,, Xueer Qiu, M.S.,, Najla Alotaibi, M.D.,, Areej Alkahtani, M.D.,, Sofija Buta, M.S.,, Emmanuelle Jouanguy, Ph.D.,, Ayman Al-Eyadhy, M.D.,, Conor Gruber, B.S.,, Gamal M. Hasan, M.D.,, Fahad A. Bashiri, M.D.,, Rabih Halwani, Ph.D.,, Hamdy H. Hassan, M.D.,, Saleh Al-Muhsen, M.D.,, Nouf Alkhamis, M.D.,, Zobaida Alsum, M.D.,, Jean-Laurent Casanova, M.D., Ph.D.,, Jacinta Bustamante, M.D., Ph.D.,, Dusan Bogunovic, Ph.D.,, and Abdullah A. Alangari, M.D.

Issue&Volume: 2020-01-15

Abstract: Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on USP18. The encoded protein was expressed but devoid of negative regulatory ability. Treatment with ruxolitinib was followed by a prompt and sustained recovery.

DOI: 10.1056/NEJMoa1905633

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1905633