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Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation

Lookup NU author(s): Dr Christopher Bacon, Dr Mario Abinun

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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.

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Abstract

© 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.


Publication metadata

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

Journal: Science

Year: 2018

Volume: 361

Issue: 6404

Pages: 810-813

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

URL: https://doi.org/10.1126/science.aar2641

DOI: 10.1126/science.aar2641


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