Publication
Inherited p40phox deficiency differs from classic chronic granulomatous disease
| dc.contributor.author | van de Geer, A. | |
| dc.contributor.author | Nieto-Patlán, A. | |
| dc.contributor.author | Kuhns, D. | |
| dc.contributor.author | Tool, A. | |
| dc.contributor.author | Arias, A. | |
| dc.contributor.author | Bouaziz, M. | |
| dc.contributor.author | de Boer, M. | |
| dc.contributor.author | Franco, J. | |
| dc.contributor.author | Gazendam, R. | |
| dc.contributor.author | van Hamme, J. | |
| dc.contributor.author | van Houdt, M. | |
| dc.contributor.author | van Leeuwen, K. | |
| dc.contributor.author | Verkuijlen, P. | |
| dc.contributor.author | van den Berg, T. | |
| dc.contributor.author | Alzate, J. | |
| dc.contributor.author | Arango-Franco, C. | |
| dc.contributor.author | Batura, V. | |
| dc.contributor.author | Bernasconi, A. | |
| dc.contributor.author | Boardman, B. | |
| dc.contributor.author | Booth, C. | |
| dc.contributor.author | Burns, S. | |
| dc.contributor.author | Cabarcas, . | |
| dc.contributor.author | Bensussan, N. | |
| dc.contributor.author | Charbit-Henrion, F. | |
| dc.contributor.author | Corveleyn, A. | |
| dc.contributor.author | Deswarte, C. | |
| dc.contributor.author | Azcoiti, M. | |
| dc.contributor.author | Foell, D. | |
| dc.contributor.author | Gallin, J. | |
| dc.contributor.author | Garcés, C. | |
| dc.contributor.author | Guedes, M. | |
| dc.contributor.author | Hinze, C. | |
| dc.contributor.author | Holland, S. | |
| dc.contributor.author | Hughes, S. | |
| dc.contributor.author | Ibañez, P. | |
| dc.contributor.author | Malech, H. | |
| dc.contributor.author | Meyts, I. | |
| dc.contributor.author | Moncada-Velez, M. | |
| dc.contributor.author | Moriya, K. | |
| dc.contributor.author | Neves, E. | |
| dc.contributor.author | Oleastro, M. | |
| dc.contributor.author | Perez, L. | |
| dc.contributor.author | Rattina, V. | |
| dc.contributor.author | Oleaga-Quintas, C. | |
| dc.contributor.author | Warner, N. | |
| dc.contributor.author | Muise, A. | |
| dc.contributor.author | López, J. | |
| dc.contributor.author | Trindade, E. | |
| dc.contributor.author | Vasconcelos, J. | |
| dc.contributor.author | Vermeire, S. | |
| dc.contributor.author | Wittkowski, H. | |
| dc.contributor.author | Worth, A. | |
| dc.contributor.author | Abel, L. | |
| dc.contributor.author | Dinauer, M. | |
| dc.contributor.author | Arkwright, P. | |
| dc.contributor.author | Roos, D. | |
| dc.contributor.author | Casanova, J.t | |
| dc.contributor.author | Kuijpers, T. | |
| dc.contributor.author | Bustamante, J. | |
| dc.date.accessioned | 2019-11-14T15:35:12Z | |
| dc.date.available | 2019-11-14T15:35:12Z | |
| dc.date.issued | 2018-08-31 | |
| dc.description.abstract | 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. | pt_PT |
| dc.description.version | info:eu-repo/semantics/publishedVersion | pt_PT |
| dc.identifier.citation | J Clin Invest. 2018 Aug 31;128(9):3957-3975 | pt_PT |
| dc.identifier.doi | 10.1172/JCI97116 | pt_PT |
| dc.identifier.issn | 0021-9738 | |
| dc.identifier.issn | 1558-8238 | |
| dc.identifier.uri | http://hdl.handle.net/10400.16/2297 | |
| dc.language.iso | eng | pt_PT |
| dc.peerreviewed | yes | pt_PT |
| dc.publisher | American Society for Clinical Investigation | pt_PT |
| dc.relation.publisherversion | https://www.jci.org/articles/view/97116/pdf | pt_PT |
| dc.subject | Genetics | pt_PT |
| dc.subject | Immunology | pt_PT |
| dc.subject | Inflammatory bowel disease | pt_PT |
| dc.subject | Macrophages | pt_PT |
| dc.subject | Neutrophils | pt_PT |
| dc.title | Inherited p40phox deficiency differs from classic chronic granulomatous disease | pt_PT |
| dc.type | journal article | |
| dspace.entity.type | Publication | |
| oaire.citation.conferencePlace | United States of America | pt_PT |
| oaire.citation.endPage | 3975 | pt_PT |
| oaire.citation.issue | 9 | pt_PT |
| oaire.citation.startPage | 3957 | pt_PT |
| oaire.citation.title | Journal of Clinical Investigation | pt_PT |
| oaire.citation.volume | 128 | pt_PT |
| rcaap.rights | openAccess | pt_PT |
| rcaap.type | article | pt_PT |