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

Cuchet-Lourenço, D; Eletto, D; Wu, C; Plagnol, V; Papapietro, O; Curtis, J; Ceron-Gutierrez, L; ... Nejentsev, S; + view all (2018) Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation. Science , 361 (6404) pp. 810-813. 10.1126/science.aar2641. Green open access

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Abstract

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.

Type: Article
Title: Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1126/science.aar2641
Publisher version: https://doi.org/10.1126/science.aar2641
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alleles, Arthritis, Cytokines, Female, Fibroblasts, Humans, Inflammatory Bowel Diseases, Lymphopenia, Male, Mitogen-Activated Protein Kinases, Pedigree, Receptor-Interacting Protein Serine-Threonine Kinases, Severe Combined Immunodeficiency
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
URI: https://discovery.ucl.ac.uk/id/eprint/10062945
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