Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients.
Identifieur interne : 000086 ( PubMed/Curation ); précédent : 000085; suivant : 000087Acquired 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 GATA2 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.
DOI: 10.3389/fimmu.2017.00802
PubMed: 28747912
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Rodríguez-Vigil</name><affiliation wicri:level="1"><nlm:affiliation>Servicio de Hemato-Oncología Pediátrica, Hospital Universitario Miguel Servet, Zaragoza, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Hemato-Oncología Pediátrica, Hospital Universitario Miguel Servet, Zaragoza</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:affiliation>Sección de Inmunología, Hospital General Universitario de Alicante, Alicante, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Sección de Inmunología, Hospital General Universitario de Alicante, Alicante</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:affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid</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:affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid</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:affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid</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:affiliation>Sección de Inmunología, Hospital General Universitario de Alicante, Alicante, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Sección de Inmunología, Hospital General Universitario de Alicante, Alicante</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:affiliation>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid</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:affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid</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:affiliation>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid</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:affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</nlm:affiliation><country xml:lang="fr">Espagne</country><wicri:regionArea>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in immunology</title><idno type="ISSN">1664-3224</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">GATA binding protein 2 (GATA2) deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the GATA2 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.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">28747912</PMID><DateCreated><Year>2017</Year><Month>07</Month><Day>27</Day></DateCreated><DateRevised><Year>2017</Year><Month>07</Month><Day>30</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Print">1664-3224</ISSN><JournalIssue CitedMedium="Print"><Volume>8</Volume><PubDate><Year>2017</Year></PubDate></JournalIssue><Title>Frontiers in immunology</Title><ISOAbbreviation>Front Immunol</ISOAbbreviation></Journal><ArticleTitle>Acquired Senescent T-Cell Phenotype Correlates with Clinical Severity in GATA Binding Protein 2-Deficient Patients.</ArticleTitle><Pagination><MedlinePgn>802</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3389/fimmu.2017.00802</ELocationID><Abstract><AbstractText>GATA binding protein 2 (GATA2) deficiency is a rare disorder of hematopoiesis, lymphatics, and immunity caused by spontaneous or autosomal dominant mutations in the GATA2 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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ruiz-García</LastName><ForeName>Raquel</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rodríguez-Vigil</LastName><ForeName>Carmen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Servicio de Hemato-Oncología Pediátrica, Hospital Universitario Miguel Servet, Zaragoza, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marco</LastName><ForeName>Francisco Manuel</ForeName><Initials>FM</Initials><AffiliationInfo><Affiliation>Sección de Inmunología, Hospital General Universitario de Alicante, Alicante, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gallego-Bustos</LastName><ForeName>Fernando</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Castro-Panete</LastName><ForeName>María José</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Diez-Alonso</LastName><ForeName>Laura</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Muñoz-Ruiz</LastName><ForeName>Carlos</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Sección de Inmunología, Hospital General Universitario de Alicante, Alicante, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ruiz-Contreras</LastName><ForeName>Jesús</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Unidad de Inmunodeficiencias, Servicio de Pediatría, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Paz-Artal</LastName><ForeName>Estela</ForeName><Initials>E</Initials><AffiliationInfo><Affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Sección de Inmunología, Universidad de San Pablo CEU, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>González-Granado</LastName><ForeName>Luis Ignacio</ForeName><Initials>LI</Initials><AffiliationInfo><Affiliation>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Unidad de Inmunodeficiencias, Servicio de Pediatría, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Allende</LastName><ForeName>Luis Miguel</ForeName><Initials>LM</Initials><AffiliationInfo><Affiliation>Servicio de Inmunología, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Instituto de Investigación I+12, Hospital Universitario 12 de Octubre, Madrid, Spain.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2017</Year><Month>07</Month><Day>12</Day></ArticleDate></Article><MedlineJournalInfo><Country>Switzerland</Country><MedlineTA>Front Immunol</MedlineTA><NlmUniqueID>101560960</NlmUniqueID><ISSNLinking>1664-3224</ISSNLinking></MedlineJournalInfo><CommentsCorrectionsList><CommentsCorrections RefType="Cites"><RefSource>J Immunol. 2008 Mar 15;180(6):3739-45</RefSource><PMID Version="1">18322179</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Clin 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Version="1">18785267</PMID></CommentsCorrections></CommentsCorrectionsList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">GATA binding protein 2</Keyword><Keyword MajorTopicYN="N">T-cell</Keyword><Keyword MajorTopicYN="N">myelodysplastic syndrome</Keyword><Keyword MajorTopicYN="N">natural killer-cell</Keyword><Keyword MajorTopicYN="N">primary immunodeficiency</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2017</Year><Month>04</Month><Day>06</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2017</Year><Month>06</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2017</Year><Month>7</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2017</Year><Month>7</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2017</Year><Month>7</Month><Day>28</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>epublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">28747912</ArticleId><ArticleId IdType="doi">10.3389/fimmu.2017.00802</ArticleId><ArticleId IdType="pmc">PMC5506090</ArticleId></ArticleIdList></PubmedData></pubmed></record>Pour manipuler ce document sous Unix (Dilib)
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