IRF8 Mutations and Human Dendritic-Cell Immunodeficiency

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dc.contributor.authorHambleton, Sophie
dc.contributor.authorSalem, Sandra
dc.contributor.authorBustamante, Jacinta
dc.contributor.authorBigley, Venetia
dc.contributor.authorBoisson Dupuis, Stephanie
dc.contributor.authorAzevedo, Joana
dc.contributor.authorFortin, Anny
dc.contributor.authorHaniffa, Muzlifah
dc.contributor.authorCeron Gutierrez, Lourdes
dc.contributor.authorBacon, Chris M.
dc.contributor.authorMenon, Geetha
dc.contributor.authorTrouillet, Celine
dc.contributor.authorMcDonald, David
dc.contributor.authorCarey, Peter
dc.contributor.authorGinhoux, Florent
dc.contributor.authorAlsina, Laia
dc.contributor.authorZumwalt, Timothy J.
dc.contributor.authorKong, Xiao Fei
dc.contributor.authorKumararatne, Dinakantha
dc.contributor.authorButler, Karina
dc.contributor.authorHubeau, Marjorie
dc.contributor.authorFeinberg, Jacqueline
dc.contributor.authorAl Muhsen, Saleh
dc.contributor.authorCant, Andrew
dc.contributor.authorAbel, Laurent
dc.contributor.authorChaussabel, Damien
dc.contributor.authorDoffinger, Rainer
dc.contributor.authorTalesnik, Eduardo
dc.contributor.authorGrumach, Anete
dc.contributor.authorDuarte, Alberto
dc.contributor.authorAbarca, Katia
dc.contributor.authorMoraes Vasconcelos, Dewton
dc.contributor.authorBurk, David
dc.contributor.authorBerghuis, Albert
dc.contributor.authorGeissmann, Frederic
dc.contributor.authorCollin, Matthew
dc.contributor.authorCasanova, Jean Laurent
dc.contributor.authorGros, Philippe
dc.date.accessioned2024-01-10T12:39:54Z
dc.date.available2024-01-10T12:39:54Z
dc.date.issued2011
dc.description.abstractBACKGROUND
dc.description.abstractThe genetic analysis of human primary immunodeficiencies has defined the contribution of specific cell populations and molecular pathways in the host defense against infection. Disseminated infection caused by bacille Calmette-Guerin (BCG) vaccines is an early manifestation of primary immunodeficiencies, such as severe combined immunodeficiency. In many affected persons, the cause of disseminated BCG disease is unexplained.
dc.description.abstractMETHODS
dc.description.abstractWe evaluated an infant presenting with features of severe immunodeficiency, including early-onset disseminated BCG disease, who required hematopoietic stem-cell transplantation. We also studied two otherwise healthy subjects with a history of disseminated but curable BCG disease in childhood. We characterized the monocyte and dendritic-cell compartments in these three subjects and sequenced candidate genes in which mutations could plausibly confer susceptibility to BCG disease.
dc.description.abstractRESULTS
dc.description.abstractWe detected two distinct disease-causing mutations affecting interferon regulatory factor 8 (IRF8). Both K108E and T80A mutations impair IRF8 transcriptional activity by disrupting the interaction between IRF8 and DNA. The K108E variant was associated with an autosomal recessive severe immunodeficiency with a complete lack of circulating monocytes and dendritic cells. The T80A variant was associated with an autosomal dominant, milder immunodeficiency and a selective depletion of CD11c+CD1c+ circulating dendritic cells.
dc.description.abstractCONCLUSIONS
dc.description.abstractThese findings define a class of human primary immunodeficiencies that affect the differentiation of mononuclear phagocytes. They also show that human IRF8 is critical for the development of monocytes and dendritic cells and for antimycobacterial immunity. (Funded by the Medical Research Council and others.)
dc.description.funderMedical Research Council
dc.description.funderNational Institutes of Health
dc.description.funderCanadian Institutes of Health Research
dc.description.funderAgence Nationale de la Recherche (ANR)
dc.description.funderSt. Giles Foundation
dc.description.funderJeffrey Modell Foundation
dc.description.funderTalecris Biotherapeutics
dc.description.funderRockefeller University Center for Clinical and Translational Science
dc.description.funderEuropean Union
dc.description.funderMarch of Dimes
dc.description.funderWellcome Trust
dc.description.funderLeukaemia and Lymphoma Research Fund
dc.description.funderArthritis Research UK Chair in Inflammation Biology
dc.description.funderMedical Research Council
dc.description.funderEuropean Research Council
dc.description.funderFundacao Calouste Gulbenkian
dc.description.funderFundacao Champalimaud
dc.description.funderMinisterio da Saude e Fundacao para a Ciencia e Tecnologia, Portugal
dc.description.funderNATIONAL CENTER FOR RESEARCH RESOURCES
dc.description.funderNATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent12 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1056/NEJMoa1100066
dc.identifier.issn0028-4793
dc.identifier.pubmedidMEDLINE:21524210
dc.identifier.urihttps://doi.org/10.1056/NEJMoa1100066
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/77247
dc.identifier.wosidWOS:000292685500009
dc.information.autorucMedicina;Abarca K ;S/I;70281
dc.information.autorucMedicina;Talesnik E;S/I;99067
dc.issue.numero2
dc.language.isoen
dc.nota.accesocontenido parcial
dc.pagina.final138
dc.pagina.inicio127
dc.publisherMASSACHUSETTS MEDICAL SOC
dc.revistaNEW ENGLAND JOURNAL OF MEDICINE
dc.rightsacceso restringido
dc.subjectREGULATORY FACTOR-8
dc.subjectMOUSE
dc.subjectICSBP
dc.subjectTUBERCULOSIS
dc.subjectMACROPHAGES
dc.subjectRESPONSES
dc.subjectIMMUNITY
dc.subjectREVEALS
dc.subjectBINDING
dc.subjectMICE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleIRF8 Mutations and Human Dendritic-Cell Immunodeficiency
dc.typeartículo
dc.volumen365
sipa.codpersvinculados70281
sipa.codpersvinculados99067
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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