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.
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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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