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dc.contributor.author
Sampaio, Elizabeth P.
dc.contributor.author
Hsu, Amy P.
dc.contributor.author
Pechacek, Joseph
dc.contributor.author
Hannelore I.
dc.contributor.author
Dias, Dalton L.
dc.contributor.author
Paulson, Michelle L.
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Chandrasekaran, Prabha
dc.contributor.author
Rosen, Lindsey B.
dc.contributor.author
Carvalho, Daniel S.
dc.contributor.author
Ding, Li
dc.contributor.author
Vinh, Donald C.
dc.contributor.author
Browne, Sarah K.
dc.contributor.author
Datta, Shrimati
dc.contributor.author
Milner, Joshua D.
dc.contributor.author
Kuhns, Douglas B.
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Long Priel, Debra A.
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Sadat, Mohammed A.
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Shiloh, Michael
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De Marco, Brendan
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Alvares, Michael
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Gillman, Jason W.
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Ramarathnam, Vivek
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de la Morena, Maite
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Bezrodnik, Liliana
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Moreira, Ileana
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Uzel, Gulbu
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Johnson, Daniel
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Spalding, Christine
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Zerbe, Christa S.
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Wiley, Henry
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Greenberg, David E.
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Hoover, Susan E.
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Rosenzweig, Sergio D.
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Galgiani, John N.
dc.contributor.author
Holland, Steven M.
dc.date.available
2016-01-20T20:22:40Z
dc.date.issued
2013-03-28
dc.identifier.citation
Sampaio, Elizabeth P.; Hsu, Amy P.; Pechacek, Joseph; Hannelore I.; Dias, Dalton L.; et al.; Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis; Elsevier; Journal of Allergy and Clinical Immunology; 131; 6; 28-3-2013; 1624-1634
dc.identifier.issn
0091-6749
dc.identifier.uri
http://hdl.handle.net/11336/3707
dc.description.abstract
Background: Impaired signaling in the IFN-g/IL-12 pathway causes susceptibility to severe disseminated infections with mycobacteria and dimorphic yeasts. Dominant gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1) have been associated with chronic mucocutaneous candidiasis.
Objective: We sought to identify the molecular defect in patients with disseminated dimorphic yeast infections.
Methods: PBMCs, EBV-transformed B cells, and transfected U3A cell lines were studied for IFN-g/IL-12 pathway function. STAT1 was sequenced in probands and available relatives. Interferon-induced STAT1 phosphorylation, transcriptional responses, protein-protein interactions, target gene activation, and function were investigated.
Results: We identified 5 patients with disseminated Coccidioides immitis or Histoplasma capsulatum with heterozygous missense mutations in the STAT1 coiled-coil or DNA-binding domains. These are dominant gain-of-function mutations causing enhanced STAT1 phosphorylation, delayed dephosphorylation, enhanced DNA binding and transactivation, and enhanced interaction with protein inhibitor of activated STAT1. The mutations caused enhanced IFN-g–induced gene expression, but we found impaired responses to IFN-g restimulation.
Conclusion: Gain-of-function mutations in STAT1 predispose to invasive, severe, disseminated dimorphic yeast infections, likely through aberrant regulation of IFN-g–mediated inflammation
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Ifn-G
dc.subject
Histoplasma
dc.subject
Signal Transducer And Activator of Transcription 1
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Progressive Multifocal Leukoencephalopathy
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Enfermedades Infecciosas
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations and disseminated coccidioidomycosis and histoplasmosis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
131
dc.journal.number
6
dc.journal.pagination
1624-1634
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
Fil: Sampaio, Elizabeth P.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos. Instituto Oswaldo Cruz. Laboratorio de Leprologia; Brasil
dc.description.fil
Fil: Hsu, Amy P.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
dc.description.fil
Fil: Pechacek, Joseph. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
dc.description.fil
Fil: Hannelore I.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos. Erasmus Medical Center. Department of Medical Microbiology and Infectious Disease; Países Bajos
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Fil: Dias, Dalton L.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
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Fil: Paulson, Michelle L.. Clinical Research Directorate/CMRP; Estados Unidos
dc.description.fil
Fil: Chandrasekaran, Prabha. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
dc.description.fil
Fil: Rosen, Lindsey B.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
dc.description.fil
Fil: Carvalho, Daniel S.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos. Instituto Oswaldo Cruz, Laboratorio de Leprologia; Brasil
dc.description.fil
Fil: Ding, Li. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
dc.description.fil
Fil: Vinh, Donald C.. McGill University Health Centre. Division of Infectious Diseases; Canadá
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Fil: Browne, Sarah K.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
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Fil: Datta, Shrimati. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Allergic Diseases. Allergic Inflammation Unit; Estados Unidos
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Fil: Milner, Joshua D.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Allergic Diseases. Allergic Inflammation Unit; Estados Unidos
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Fil: Kuhns, Douglas B.. Clinical Services Program; Estados Unidos
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Fil: Long Priel, Debra A.. Clinical Services Program; Estados Unidos
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Fil: Sadat, Mohammed A.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Host Defenses. Infectious Diseases Susceptibility Unit; Estados Unidos
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Fil: Shiloh, Michael. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados Unidos
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Fil: De Marco, Brendan. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados Unidos
dc.description.fil
Fil: Alvares, Michael. University of Texas. Southwestern Medical Center. Division of Allergy and Immunology; Estados Unidos
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Fil: Gillman, Jason W.. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados Unidos
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Fil: Ramarathnam, Vivek. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados Unidos
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Fil: de la Morena, Maite. University of Texas. Southwestern Medical Center. Division of Allergy and Immunology; Estados Unidos
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Fil: Bezrodnik, Liliana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutierrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
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Fil: Moreira, Ileana. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutierrez"; Argentina
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Fil: Uzel, Gulbu. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
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Fil: Johnson, Daniel. University of Chicago. Comer Children; Estados Unidos
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Fil: Spalding, Christine. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
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Fil: Zerbe, Christa S.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
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Fil: Wiley, Henry. National Eye Institute. Clinical Trials Branch; Estados Unidos
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Fil: Greenberg, David E.. University of Texas. Southwestern Medical Center. Division of Infectious Diseases; Estados Unidos
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Fil: Hoover, Susan E.. University of Arizona. College of Medicine. Valley Fever Center for Excellence; Estados Unidos
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Fil: Rosenzweig, Sergio D.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Host Defenses Infectious Diseases Susceptibility Unit; Estados Unidos. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Primary Immunodeficiency Clinic; Estados Unidos
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Fil: Galgiani, John N.. University of Arizona. College of Medicine. Valley Fever Center for Excellence; Estados Unidos
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Fil: Holland, Steven M.. National Institutes of Health. National Institute of Allergy and Infectious Diseases. Laboratory of Clinical Infectious Diseases. Immunopathogenesis Section; Estados Unidos
dc.journal.title
Journal of Allergy and Clinical Immunology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0091674913002650
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.jaci.2013.01.052
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3746066/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/0091-6749
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