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Inherited p40phox deficiency differs from classic chronic granulomatous disease

dc.contributor.authorvan de Geer, A.
dc.contributor.authorNieto-Patlán, A.
dc.contributor.authorKuhns, D.
dc.contributor.authorTool, A.
dc.contributor.authorArias, A.
dc.contributor.authorBouaziz, M.
dc.contributor.authorde Boer, M.
dc.contributor.authorFranco, J.
dc.contributor.authorGazendam, R.
dc.contributor.authorvan Hamme, J.
dc.contributor.authorvan Houdt, M.
dc.contributor.authorvan Leeuwen, K.
dc.contributor.authorVerkuijlen, P.
dc.contributor.authorvan den Berg, T.
dc.contributor.authorAlzate, J.
dc.contributor.authorArango-Franco, C.
dc.contributor.authorBatura, V.
dc.contributor.authorBernasconi, A.
dc.contributor.authorBoardman, B.
dc.contributor.authorBooth, C.
dc.contributor.authorBurns, S.
dc.contributor.authorCabarcas, .
dc.contributor.authorBensussan, N.
dc.contributor.authorCharbit-Henrion, F.
dc.contributor.authorCorveleyn, A.
dc.contributor.authorDeswarte, C.
dc.contributor.authorAzcoiti, M.
dc.contributor.authorFoell, D.
dc.contributor.authorGallin, J.
dc.contributor.authorGarcés, C.
dc.contributor.authorGuedes, M.
dc.contributor.authorHinze, C.
dc.contributor.authorHolland, S.
dc.contributor.authorHughes, S.
dc.contributor.authorIbañez, P.
dc.contributor.authorMalech, H.
dc.contributor.authorMeyts, I.
dc.contributor.authorMoncada-Velez, M.
dc.contributor.authorMoriya, K.
dc.contributor.authorNeves, E.
dc.contributor.authorOleastro, M.
dc.contributor.authorPerez, L.
dc.contributor.authorRattina, V.
dc.contributor.authorOleaga-Quintas, C.
dc.contributor.authorWarner, N.
dc.contributor.authorMuise, A.
dc.contributor.authorLópez, J.
dc.contributor.authorTrindade, E.
dc.contributor.authorVasconcelos, J.
dc.contributor.authorVermeire, S.
dc.contributor.authorWittkowski, H.
dc.contributor.authorWorth, A.
dc.contributor.authorAbel, L.
dc.contributor.authorDinauer, M.
dc.contributor.authorArkwright, P.
dc.contributor.authorRoos, D.
dc.contributor.authorCasanova, J.t
dc.contributor.authorKuijpers, T.
dc.contributor.authorBustamante, J.
dc.date.accessioned2019-11-14T15:35:12Z
dc.date.available2019-11-14T15:35:12Z
dc.date.issued2018-08-31
dc.description.abstractBiallelic 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Clin Invest. 2018 Aug 31;128(9):3957-3975pt_PT
dc.identifier.doi10.1172/JCI97116pt_PT
dc.identifier.issn0021-9738
dc.identifier.issn1558-8238
dc.identifier.urihttp://hdl.handle.net/10400.16/2297
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherAmerican Society for Clinical Investigationpt_PT
dc.relation.publisherversionhttps://www.jci.org/articles/view/97116/pdfpt_PT
dc.subjectGeneticspt_PT
dc.subjectImmunologypt_PT
dc.subjectInflammatory bowel diseasept_PT
dc.subjectMacrophagespt_PT
dc.subjectNeutrophilspt_PT
dc.titleInherited p40phox deficiency differs from classic chronic granulomatous diseasept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.conferencePlaceUnited States of Americapt_PT
oaire.citation.endPage3975pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage3957pt_PT
oaire.citation.titleJournal of Clinical Investigationpt_PT
oaire.citation.volume128pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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