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dc.contributor.authorCuchet-Lourenço, Delphine
dc.contributor.authorEletto, Davide
dc.contributor.authorWu, Changxin
dc.contributor.authorPlagnol, Vincent
dc.contributor.authorPapapietro, Olivier
dc.contributor.authorCurtis, James
dc.contributor.authorCeron-Gutierrez, Lourdes
dc.contributor.authorBacon, Chris M
dc.contributor.authorHackett, Scott
dc.contributor.authorAlsaleem, Badr
dc.contributor.authorMaes, Mailis
dc.contributor.authorGaspar, Miguel
dc.contributor.authorAlisaac, Ali
dc.contributor.authorGoss, Emma
dc.contributor.authorAlIdrissi, Eman
dc.contributor.authorSiegmund, Daniela
dc.contributor.authorWajant, Harald
dc.contributor.authorKumararatne, Dinakantha
dc.contributor.authorAlZahrani, Mofareh S
dc.contributor.authorArkwright, Peter D
dc.contributor.authorAbinun, Mario
dc.contributor.authorDoffinger, Rainer
dc.contributor.authorNejentsev, Sergey
dc.date.accessioned2018-09-08T06:33:53Z
dc.date.available2018-09-08T06:33:53Z
dc.date.issued2018-08-24
dc.identifier.issn0036-8075
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/279895
dc.description.abstractRIPK1 (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.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Association for the Advancement of Science (AAAS)
dc.subjectFibroblasts
dc.subjectHumans
dc.subjectArthritis
dc.subjectInflammatory Bowel Diseases
dc.subjectLymphopenia
dc.subjectSevere Combined Immunodeficiency
dc.subjectMitogen-Activated Protein Kinases
dc.subjectCytokines
dc.subjectPedigree
dc.subjectAlleles
dc.subjectFemale
dc.subjectMale
dc.subjectReceptor-Interacting Protein Serine-Threonine Kinases
dc.titleBiallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.
dc.typeArticle
prism.endingPage813
prism.issueIdentifier6404
prism.publicationDate2018
prism.publicationNameScience
prism.startingPage810
prism.volume361
dc.identifier.doi10.17863/CAM.27263
dcterms.dateAccepted2018-06-28
rioxxterms.versionofrecord10.1126/science.aar2641
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08
dc.contributor.orcidCuchet-Lourenço, Delphine [0000-0002-9501-6122]
dc.contributor.orcidEletto, Davide [0000-0002-2650-1968]
dc.contributor.orcidPlagnol, Vincent [0000-0002-5597-9215]
dc.contributor.orcidPapapietro, Olivier [0000-0001-5072-5235]
dc.contributor.orcidBacon, Chris M [0000-0002-8268-2812]
dc.contributor.orcidAlsaleem, Badr [0000-0003-3348-4550]
dc.contributor.orcidMaes, Mailis [0000-0002-0266-6557]
dc.contributor.orcidAlisaac, Ali [0000-0003-1463-4488]
dc.contributor.orcidGoss, Emma [0000-0002-5277-4249]
dc.contributor.orcidAlIdrissi, Eman [0000-0003-2462-3571]
dc.contributor.orcidWajant, Harald [0000-0002-2005-3949]
dc.contributor.orcidKumararatne, Dinakantha [0000-0001-8438-4686]
dc.contributor.orcidArkwright, Peter D [0000-0002-7411-5375]
dc.contributor.orcidAbinun, Mario [0000-0002-7050-3565]
dc.contributor.orcidDoffinger, Rainer [0000-0002-9841-3617]
dc.contributor.orcidNejentsev, Sergey [0000-0002-7528-4461]
dc.identifier.eissn1095-9203
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/M012328/1)
pubs.funder-project-idWellcome Trust (095198/Z/10/Z)
pubs.funder-project-idEuropean Research Council (260477)
cam.issuedOnline2018-07-19
rioxxterms.freetoread.startdate2019-08-31


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