Skip NavigationSkip to Content
Return Return to Search Results

Inherited p40(phox) deficiency differs from classic chronic granulomatous disease

  1. Author:
    van de Geer, Annemarie
    Nieto-Patlan, Alejandro
    Kuhns, Doug
    Tool, Anton T. J.
    Arias, Andres A.
    Bouaziz, Matthieu
    de Boer, Martin
    Luis Franco, Jose
    Gazendam, Roel P.
    van Hamme, John L.
    van Houdt, Michel
    van Leeuwen, Karin
    Verkuijlen, Paul J. H.
    van den Berg, Timo K.
    Alzate, Juan F.
    Arango-Franco, Carlos A.
    Batura, Vritika
    Bernasconi, Andrea R.
    Boardman, Barbara
    Booth, Claire
    Burns, Siobhan O.
    Cabarcas, Felipe
    Bensussan, Nadine Cerf
    Charbit-Henrion, Fabienne
    Corveleyn, Anniek
    Deswarte, Caroline
    Esnaola Azcoiti, Maria
    Foell, Dirk
    Gallin, John I.
    Garces, Carlos
    Guedes, Margarida
    Hinze, Claas H.
    Holland, Steven M.
    Hughes, Stephen M.
    Ibanez, Patricio
    Malech, Harry L.
    Meyts, Isabelle
    Moncada-Velez, Marcela
    Moriya, Kunihiko
    Neves, Esmeralda
    Oleastro, Matias
    Perez, Laura
    Rattina, Vimel
    Oleaga-Quintas, Carmen
    Warner, Neil
    Muise, Aleixo M.
    Serafin Lopez, Jeanet
    Trindade, Eunice
    Vasconcelos, Julia
    Vermeire, Severine
    Wittkowski, Helmut
    Worth, Austen
    Abel, Laurent
    Dinauer, Mary C.
    Arkwright, Peter D.
    Roos, Dirk
    Casanova, Jean-Laurent
    Kuijpers, Taco W.
    Bustamante, Jacinta

  2. Author Address

    Univ Amsterdam, Acad Med Ctr, Sanquin Res, Dept Blood Cell Res, Amsterdam, Netherlands.Necker Hosp Sick Children, Lab Human Genet Infect Dis, Necker Branch, INSERM,U1163, Paris, France.Paris Descartes Univ, Imagine Inst, Paris, France.IPN, ENCB, Natl Polytech Inst, Dept Immunol,Natl Sch Biol Sci, Mexico City, DF, Mexico.Frederick Natl Lab Canc Res, Neutrophil Monitoring Lab, Clin Serv Program, Leidos Biomed Res Inc, Frederick, MD USA.Univ Antioquia, Sch Med, Dept Microbiol & Parasitol, Primary Immunodeficiencies Grp, Medellin, Colombia.Univ Antioquia, Sch Microbiol, Medellin, Colombia.Vrije Univ Amsterdam, VU Med Ctr, Dept Mol Cell Biol & Immunol, Amsterdam, Netherlands.Univ Antioquia, Sch Med, SIU, Natl Ctr Genom Sequencing,CNSG, Medellin, Colombia.Univ Toronto, Hosp Sick Children, Dept Pediat & Biochem, Toronto, ON, Canada.Garrahan Natl Pediat Hosp, Serv Immunol & Rheumatol, Buenos Aires, DF, Argentina.Univ Manchester, Royal Manchester Childrens Hosp, Dept Pediat Allergy & Immunol, Manchester, Lancs, England.NHS Fdn Trust, Great Ormond St Hosp, Dept Immunol, London, England.UCL, Inst Immun & Transplantat, London, England.NHS Fdn Trust, Royal Free London, Dept Clin Immunol, London, England.Univ Antioquia, Dept Elect Engn, SISTEM Grp, Medellin, Colombia.INSERM, Lab Intestinal Immun, U1163, Imagine Inst, Paris, France.European Soc Pediat Gastroenterol Hepatol & Nutr, GENIUS Grp GENet ImmUne Mediated EnteropathieS, Paris, France.Paris Descartes Univ, Paris, France.Necker Hosp Sick Children, AP HP, Pediat Gastroenterol Hepatol & Nutr Unit, Paris, France.Univ Hosp Leuven, Dept Human Genet, Leuven, Belgium.Ricardo Gutierrez Childrens Hosp, Dept Immunol, Buenos Aires, DF, Argentina.Munster Univ Hosp, Dept Pediat Rheumatol & Immunol, Munster, Germany.NIAID, Lab Clin Immunol & Microbiol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.Santo Antonio Hosp, Dept Pediat, Porto, Portugal.NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.Univ Chile, Clin Los Condes Med Ctr, Dept Gastroenterol, Inflammatory Bowel Dis Program, Santiago, Chile.Katholieke Univ Leuven, Univ Hosp Leuven, Dept Pediat Hematol & Oncol, Leuven, Belgium.Katholieke Univ Leuven, Univ Hosp Leuven, Dept Microbiol & Immunol, Leuven, Belgium.Santo Antonio Hosp, Dept Immunol, Porto, Portugal.Univ Toronto, Hosp Sick Children, Res Inst, SickKids Inflammatory Bowel Dis Ctr, Toronto, ON, Canada.Univ Toronto, Hosp Sick Children, Res Inst, Cell Biol Program, Toronto, ON, Canada.Univ Toronto, Hosp Sick Children, Dept Pediat & Biochem, Div Gastroenterol Hepatol & Nutr, Toronto, ON, Canada.Sao Joao Hosp, Pediat Gastroenterol Unit, Porto, Portugal.Univ Hosp Leuven, Div Gastroenterol & Hepatol, Leuven, Belgium.Katholieke Univ Leuven, Dept Expt Med, Leuven, Belgium.Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, 1230 York Ave, New York, NY 10021 USA.Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA.Howard Hughes Med Inst, New York, NY USA.Necker Hosp Sick Children, AP HP, Pediat Hematol & Immunol Unit, Paris, France.Emma Childrens Hosp, Dept Pediat Hematol Immunol & Infect Dis, Amsterdam, Netherlands.Univ Amsterdam, Acad Med Ctr, Amsterdam, Netherlands.Necker Hosp Sick Children, Ctr Study Primary Immunodeficiencies, Paris, France.
    1. Year: 2018
    2. Date: Aug 31
  2. Journal: Journal of Clinical Investigation
  3. AMER SOC CLINICAL INVESTIGATION INC,
    1. 128
    2. 9
    3. Pages: 3957-3975
  5. Type of Article: Article
  6. ISSN: 0021-9738
  1. Abstract:

    Biallelic loss-of-function (LOF) mutations of the NCF4 gene, encoding the p40(phox) subunit of the phagocyte NADPH oxidase, have been described in only 1 patient. We report on 24 p40(phox)-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 PMAinduced 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 p40(phox) deficiency underlies a distinctive condition, resembling a mild, atypical form of CGD.

    See More

  1. Keywords:

External Sources

  1. View Full Text
  2. DOI: 10.1172/JCI97116
  3. View record in Web of Science®
  4. WOS: 000443283400034

Library Notes

  1. Fiscal Year: FY2017-2018
NCI at FrederickClose Button

You are leaving a government website.

This external link provides additional information that is consistent with the intended purpose of this site. The government cannot attest to the accuracy of a non-federal site.

Linking to a non-federal site does not constitute an endorsement by this institution or any of its employees of the sponsors or the information and products presented on the site. You will be subject to the destination site's privacy policy when you follow the link.

ContinueCancel