Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients
Identifieur interne : 000809 ( Main/Exploration ); précédent : 000808; suivant : 000810Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients
Auteurs : Raquel Ruiz-García [Espagne] ; Carmen Rodríguez-Vigil [Espagne] ; Francisco Manuel Marco [Espagne] ; Fernando Gallego-Bustos [Espagne] ; María José Castro-Panete [Espagne] ; Laura Diez-Alonso [Espagne] ; Carlos Mu Oz-Ruiz [Espagne] ; Jesús Ruiz-Contreras [Espagne] ; Estela Paz-Artal [Espagne] ; Luis Ignacio González-Granado [Espagne] ; Luis Miguel Allende [Espagne]Source :
- Frontiers in Immunology [ 1664-3224 ] ; 2017.
Abstract
GATA binding protein 2 (GATA2) deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the
Url:
DOI: 10.3389/fimmu.2017.00802
PubMed: 28747912
PubMed Central: 5506090
Affiliations:
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strict</wicri:regionArea></affiliation></author><author><name sortKey="Rodriguez Vigil, Carmen" sort="Rodriguez Vigil, Carmen" uniqKey="Rodriguez Vigil C" first="Carmen" last="Rodríguez-Vigil">Carmen Rodríguez-Vigil</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Servicio de Hemato-Oncología Pediátrica, Hospital Universitario Miguel Servet</institution>,<addr-line>Zaragoza</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Marco, Francisco Manuel" sort="Marco, Francisco Manuel" uniqKey="Marco F" first="Francisco Manuel" last="Marco">Francisco Manuel Marco</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Sección de Inmunología, Hospital General Universitario de Alicante</institution>,<addr-line>Alicante</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># 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type="main">Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients</title><author><name sortKey="Ruiz Garcia, Raquel" sort="Ruiz Garcia, Raquel" uniqKey="Ruiz Garcia R" first="Raquel" last="Ruiz-García">Raquel Ruiz-García</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Servicio de Inmunología, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Rodriguez Vigil, Carmen" sort="Rodriguez Vigil, Carmen" uniqKey="Rodriguez Vigil C" first="Carmen" last="Rodríguez-Vigil">Carmen Rodríguez-Vigil</name><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Servicio de Hemato-Oncología Pediátrica, Hospital Universitario Miguel Servet</institution>,<addr-line>Zaragoza</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Marco, Francisco Manuel" sort="Marco, Francisco Manuel" uniqKey="Marco F" first="Francisco Manuel" last="Marco">Francisco Manuel Marco</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Sección de Inmunología, Hospital General Universitario de Alicante</institution>,<addr-line>Alicante</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gallego Bustos, Fernando" sort="Gallego Bustos, Fernando" uniqKey="Gallego Bustos F" first="Fernando" last="Gallego-Bustos">Fernando Gallego-Bustos</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Servicio de Inmunología, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Castro Panete, Maria Jose" sort="Castro Panete, Maria Jose" uniqKey="Castro Panete M" first="María José" last="Castro-Panete">María José Castro-Panete</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Servicio de Inmunología, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Diez Alonso, Laura" sort="Diez Alonso, Laura" uniqKey="Diez Alonso L" first="Laura" last="Diez-Alonso">Laura Diez-Alonso</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Servicio de Inmunología, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Mu Oz Ruiz, Carlos" sort="Mu Oz Ruiz, Carlos" uniqKey="Mu Oz Ruiz C" first="Carlos" last="Mu Oz-Ruiz">Carlos Mu Oz-Ruiz</name><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Sección de Inmunología, Hospital General Universitario de Alicante</institution>,<addr-line>Alicante</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Ruiz Contreras, Jesus" sort="Ruiz Contreras, Jesus" uniqKey="Ruiz Contreras J" first="Jesús" last="Ruiz-Contreras">Jesús Ruiz-Contreras</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Unidad de Inmunodeficiencias, Servicio de Pediatría, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Paz Artal, Estela" sort="Paz Artal, Estela" uniqKey="Paz Artal E" first="Estela" last="Paz-Artal">Estela Paz-Artal</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Servicio de Inmunología, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Facultad de Medicina, Universidad Complutense de Madrid</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Sección de Inmunología, Universidad de San Pablo CEU</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Gonzalez Granado, Luis Ignacio" sort="Gonzalez Granado, Luis Ignacio" uniqKey="Gonzalez Granado L" first="Luis Ignacio" last="González-Granado">Luis Ignacio González-Granado</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Unidad de Inmunodeficiencias, Servicio de Pediatría, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Allende, Luis Miguel" sort="Allende, Luis Miguel" uniqKey="Allende L" first="Luis Miguel" last="Allende">Luis Miguel Allende</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Servicio de Inmunología, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre</institution>,<addr-line>Madrid</addr-line>,<country>Spain</country></nlm:aff><country xml:lang="fr">Espagne</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Immunology</title><idno type="eISSN">1664-3224</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>GATA binding protein 2 (GATA2) deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the <italic>GATA2</italic> gene. Clinical manifestations range from neutropenia, lymphedema, deafness, to severe viral and mycobacterial infections, bone marrow failure, and acute myeloid leukemia. Patients also present with monocytopenia, dendritic cell, B- and natural killer (NK)-cell deficiency. We studied the T-cell and NK-cell compartments of four GATA2-deficient patients to assess if changes in these lymphocyte populations could be correlated with clinical phenotype. Patients with more severe clinical complications demonstrated a senescent T-cell phenotype whereas patients with lower clinical score had undetectable changes relative to controls. In contrast, patients’ NK-cells demonstrated an immature/activated phenotype that did not correlate with clinical score, suggesting an intrinsic NK-cell defect. These studies will help us to determine the contribution of T- and NK-cell dysregulation to the clinical phenotype of GATA2 patients, and may help to establish the most accurate therapeutic options for these patients. Asymptomatic patients may be taken into consideration for hematopoietic stem cell transplantation when dysregulation of T-cell and NK-cell compartment is present.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Ostergaard, P" uniqKey="Ostergaard P">P Ostergaard</name></author><author><name sortKey="Simpson, Ma" uniqKey="Simpson M">MA Simpson</name></author><author><name sortKey="Connell, Fc" uniqKey="Connell F">FC Connell</name></author><author><name sortKey="Steward, Cg" uniqKey="Steward C">CG Steward</name></author><author><name sortKey="Brice, G" uniqKey="Brice G">G Brice</name></author><author><name sortKey="Woollard, Wj" uniqKey="Woollard W">WJ Woollard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kazenwadel, J" uniqKey="Kazenwadel J">J Kazenwadel</name></author><author><name sortKey="Secker, Ga" uniqKey="Secker G">GA Secker</name></author><author><name sortKey="Liu, Yj" uniqKey="Liu 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Maria Jose" sort="Castro Panete, Maria Jose" uniqKey="Castro Panete M" first="María José" last="Castro-Panete">María José Castro-Panete</name><name sortKey="Castro Panete, Maria Jose" sort="Castro Panete, Maria Jose" uniqKey="Castro Panete M" first="María José" last="Castro-Panete">María José Castro-Panete</name><name sortKey="Diez Alonso, Laura" sort="Diez Alonso, Laura" uniqKey="Diez Alonso L" first="Laura" last="Diez-Alonso">Laura Diez-Alonso</name><name sortKey="Gallego Bustos, Fernando" sort="Gallego Bustos, Fernando" uniqKey="Gallego Bustos F" first="Fernando" last="Gallego-Bustos">Fernando Gallego-Bustos</name><name sortKey="Gonzalez Granado, Luis Ignacio" sort="Gonzalez Granado, Luis Ignacio" uniqKey="Gonzalez Granado L" first="Luis Ignacio" last="González-Granado">Luis Ignacio González-Granado</name><name sortKey="Gonzalez Granado, Luis Ignacio" sort="Gonzalez Granado, Luis Ignacio" uniqKey="Gonzalez Granado L" first="Luis Ignacio" last="González-Granado">Luis Ignacio González-Granado</name><name sortKey="Marco, Francisco Manuel" sort="Marco, Francisco Manuel" uniqKey="Marco F" first="Francisco Manuel" last="Marco">Francisco Manuel Marco</name><name sortKey="Mu Oz Ruiz, Carlos" sort="Mu Oz Ruiz, Carlos" uniqKey="Mu Oz Ruiz C" first="Carlos" last="Mu Oz-Ruiz">Carlos Mu Oz-Ruiz</name><name sortKey="Paz Artal, Estela" sort="Paz Artal, Estela" uniqKey="Paz Artal E" first="Estela" last="Paz-Artal">Estela Paz-Artal</name><name sortKey="Paz Artal, Estela" sort="Paz Artal, Estela" uniqKey="Paz Artal E" first="Estela" last="Paz-Artal">Estela Paz-Artal</name><name sortKey="Paz Artal, Estela" sort="Paz Artal, Estela" uniqKey="Paz Artal E" first="Estela" last="Paz-Artal">Estela Paz-Artal</name><name sortKey="Paz Artal, Estela" sort="Paz Artal, Estela" uniqKey="Paz Artal E" first="Estela" last="Paz-Artal">Estela Paz-Artal</name><name sortKey="Rodriguez Vigil, Carmen" sort="Rodriguez Vigil, Carmen" uniqKey="Rodriguez Vigil C" first="Carmen" last="Rodríguez-Vigil">Carmen Rodríguez-Vigil</name><name sortKey="Ruiz Contreras, Jesus" sort="Ruiz Contreras, Jesus" uniqKey="Ruiz Contreras J" first="Jesús" last="Ruiz-Contreras">Jesús Ruiz-Contreras</name><name sortKey="Ruiz Contreras, Jesus" sort="Ruiz Contreras, Jesus" uniqKey="Ruiz Contreras J" first="Jesús" last="Ruiz-Contreras">Jesús Ruiz-Contreras</name><name sortKey="Ruiz Garcia, Raquel" sort="Ruiz Garcia, Raquel" uniqKey="Ruiz Garcia R" first="Raquel" last="Ruiz-García">Raquel Ruiz-García</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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