Inherited p40phox deficiency differs from classic chronic granulomatous disease

dc.creatorCabarcas Jaramillo, Felipe
dc.creatorAlzate Restrepo, Juan Fernando
dc.creatorArango Franco, Carlos Andrés
dc.creatorFranco Restrepo, José Luis
dc.creatorMoncada Vélez, Marcela
dc.creatorArias Sierra, Andrés Augusto
dc.creatorGarcés Samudio, Carlos Guillermo
dc.date2023-01-27T17:39:24Z
dc.date2023-01-27T17:39:24Z
dc.date2018
dc.date.accessioned2023-08-28T20:48:51Z
dc.date.available2023-08-28T20:48:51Z
dc.identifiervan de Geer A, Nieto-Patlán A, Kuhns DB, Tool AT, Arias AA, Bouaziz M, de Boer M, Franco JL, Gazendam RP, van Hamme JL, van Houdt M, van Leeuwen K, Verkuijlen PJ, van den Berg TK, Alzate JF, Arango-Franco CA, Batura V, Bernasconi AR, Boardman B, Booth C, Burns SO, Cabarcas F, Bensussan NC, Charbit-Henrion F, Corveleyn A, Deswarte C, Azcoiti ME, Foell D, Gallin JI, Garcés C, Guedes M, Hinze CH, Holland SM, Hughes SM, Ibañez P, Malech HL, Meyts I, Moncada-Velez M, Moriya K, Neves E, Oleastro M, Perez L, Rattina V, Oleaga-Quintas C, Warner N, Muise AM, López JS, Trindade E, Vasconcelos J, Vermeire S, Wittkowski H, Worth A, Abel L, Dinauer MC, Arkwright PD, Roos D, Casanova JL, Kuijpers TW, Bustamante J. Inherited p40phox deficiency differs from classic chronic granulomatous disease. J Clin Invest. 2018 Aug 31;128(9):3957-3975. doi: 10.1172/JCI97116.
dc.identifier0021-9738
dc.identifierhttps://hdl.handle.net/10495/33274
dc.identifier10.1172/JCI97116
dc.identifier1558-8238
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8484619
dc.descriptionABSTRACT: Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40phox subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40phox-deficient patients from 12 additional families in 8 countries. These patients display 8 different in-frame or out-of-frame mutations of NCF4 that are homozygous in 11 of the families and compound heterozygous in another. When overexpressed in NB4 neutrophil-like cells and EBV-transformed B cells in vitro, the mutant alleles were found to be LOF, with the exception of the p.R58C and c.120_134del alleles, which were hypomorphic. Particle-induced NADPH oxidase activity was severely impaired in the patients' neutrophils, whereas PMA-induced dihydrorhodamine-1,2,3 (DHR) oxidation, which is widely used as a diagnostic test for chronic granulomatous disease (CGD), was normal or mildly impaired in the patients. Moreover, the NADPH oxidase activity of EBV-transformed B cells was also severely impaired, whereas that of mononuclear phagocytes was normal. Finally, the killing of Candida albicans and Aspergillus fumigatus hyphae by neutrophils was conserved in these patients, unlike in patients with CGD. The patients suffer from hyperinflammation and peripheral infections, but they do not have any of the invasive bacterial or fungal infections seen in CGD. Inherited p40phox deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.
dc.descriptionCOL0010717
dc.descriptionCOL0007506
dc.descriptionCOL0012426
dc.format20
dc.formatapplication/pdf
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Clinical Investigation
dc.publisherGrupo de Parasitología Universidad de Antioquia
dc.publisherInmunodeficiencias Primarias
dc.publisherSistemas Embebidos e Inteligencia Computacional (SISTEMIC)
dc.publisherAnn Arbor, Estados Unidos
dc.relationJ. Clin. Invest.
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rightshttp://creativecommons.org/licenses/by-nc-sa/2.5/co/
dc.rightshttp://purl.org/coar/access_right/c_abf2
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/4.0/
dc.subjectTécnicas de Inactivación de Genes
dc.subjectGene Knockout Techniques
dc.subjectEnfermedad Granulomatosa Crónica
dc.subjectGranulomatous Disease, Chronic
dc.subjectCélulas HEK293
dc.subjectHEK293 Cells
dc.subjectMutación con Pérdida de Función
dc.subjectLoss of Function Mutation
dc.subjectProteínas Mutantes
dc.subjectMutant Proteins
dc.subjectNADPH Oxidasas
dc.subjectNADPH Oxidases
dc.subjectFagocitos
dc.subjectPhagocytes
dc.subjectFosfoproteínas
dc.subjectPhosphoproteins
dc.subjectARN Mensajero
dc.subjectRNA, Messenger
dc.subjectTransducción Genética
dc.subjectTransduction, Genetic
dc.titleInherited p40phox deficiency differs from classic chronic granulomatous disease
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.typehttp://purl.org/coar/resource_type/c_2df8fbb1
dc.typehttps://purl.org/redcol/resource_type/ART
dc.typeArtículo de investigación


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