Lookup NU author(s): Dr Christopher Bacon,
Dr Mario Abinun
This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Association for the Advancement of Science, 2018.
For re-use rights please refer to the publisher's terms and conditions.
© 2015 BMJ Publishing Group. All Rights Reserved. RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system.
Author(s): Cuchet-Lourenco D, Eletto D, Wu C, Plagnol V, Papapietro O, Curtis J, Ceron-Gutierrez L, Bacon CM, Hackett S, Alsaleem B, Maes M, Gaspar M, Alisaac A, Goss E, AlIdrissi E, Siegmund D, Wajant H, Kumararatne D, AlZahrani MS, Arkwright PD, Abinun M, Doffinger R, Nejentsev S
Publication type: Article
Publication status: Published
Online publication date: 19/07/2018
Acceptance date: 19/07/2018
Date deposited: 05/09/2018
ISSN (print): 0036-8075
ISSN (electronic): 1095-9203
Publisher: American Association for the Advancement of Science
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