Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation
Year: 2018
Type: article
Study design: Case Report
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.
Source: Science
Authors: Delphine Cuchet-Lourenço, Davide Eletto, Changxin Wu, Vincent Plagnol, Olivier Papapietro, James Curtis, Lourdes Ceron-Gutierrez, Chris M. Bacon, Scott Hackett, Badr Alsaleem, Mailis Maes, Miguel Gaspar, Ali Alisaac, Emma Goss, Eman AlIdrissi, Daniela Siegmund, Harald Wajant, Dinakantha Kumararatne, Mofareh S. AlZahrani, Peter D. Arkwright, Mario Abinun, Rainer Doffinger, Sergey Nejentsev
Institutions: University of Cambridge, University College London, Addenbrooke's Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle University, Heartlands Hospital, King Saud bin Abdulaziz University for Health Sciences, King Fahd Medical City, Universitätsklinikum Würzburg, University of Manchester, Royal Manchester Children's Hospital
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Awards: G2600702242, Genetic and functional mechanisms of susceptibility to mycobacterial infection., MICA: The Newcastle Proximity Laboratory, G6806437794, G6877642453, MICA: Fundamental Role of Phosphoinositide 3-kinase delta in Infection and Immunity: Insights from a Novel Primary Immune Deficiency Syndrome, APDS, MICA: Fundamental Role of Phosphoinositide 3-kinase delta in Infection and Immunity: Insights from a Novel Primary Immune Deficiency Syndrome, APDS
OpenAlex ID: W2883726874