Por favor, use este identificador para citar o enlazar este Item:http://hdl.handle.net/20.500.12105/20442
Título
Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56(bright) NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content
Autor(es)
Dobbs, Kerry | Tabellini, Giovanna | Calzoni, Enrica | Patrizi, Ornella | Martinez, Paula | Giliani, Silvia Clara | Moratto, Daniele | Al-Herz, Waleed | Cancrini, Caterina | Cowan, Morton | Bleesing, Jacob | Booth, Claire | Buchbinder, David | Burns, Siobhan O. | Chatila, Talal A. | Chou, Janet | Daza-Cajigal, VanessaAutor/a del sistema sanitario público de las Islas Baleares Orcid | de Bruin, Lisa M. Ott | de la Morena, MaiteTeresa | Di Matteo, Gigliola | Finocchi, Andrea | Geha, Raif | Goyal, Rakesh K. | Hayward, Anthony | Holland, Steven | Huang, Chiung-Hui | Kanariou, Maria G. | King, Alejandra | Kaplan, Blanka | Kleva, Anastasiya | Kuijpers, Taco W. | Lee, Bee Wah | Lougaris, Vassilios | Massaad, Michel | Meyts, Isabelle | Morsheimer, Megan | Neven, Benedicte | Pai, Sung-Yun | Plebani, Alessandro | Prockop, Susan | Reisli, Ismail | Soh, Jian Yi | Somech, Raz | Torgerson, Troy R. | Kim, Yae-Jaen | Walter, Jolan E. | Gennery, Andrew R. | Keles, Sevgi | Manis, John P. | Marcenaro, Emanuela | Moretta, Alessandro | Parolini, Silvia | Notarangelo, Luigi D
Fecha de publicación
2017-07-17
Cita
Dobbs K, Tabellini G, Calzoni E, Patrizi O, Martinez Bueso MP, Giliani SC, et al. Natural Killer Cells from Patients with Recombinase-Activating Gene and Non-Homologous End Joining Gene Defects Comprise a Higher Frequency of CD56(bright) NKG2A+++ Cells, and Yet Display Increased Degranulation and Higher Perforin Content. Front Immunol. 2017 Jul 17;8:798.
Idioma
Inglés
Tipo de documento
research article
Resumen
Mutations of the recombinase-activating genes 1 and 2 (RAG1 and RAG2) in humans are associated with a broad range of phenotypes. For patients with severe clinical presentation, hematopoietic stem cell transplantation (HSCT) represents the only curative treatment; however, high rates of graft failure and incomplete immune reconstitution have been observed, especially after unconditioned haploidentical transplantation. Studies in mice have shown that Rag-/-natural killer (NK) cells have a mature phenotype, reduced fitness, and increased cytotoxicity. We aimed to analyze NK cell phenotype and function in patients with mutations in RAG and in non-homologous end joining (NHEJ) genes. Here, we provide evidence that NK cells from these patients have an immature phenotype, with significant expansion of CD56(bright) CD16(-/int) CD57(-cells), yet increased degranulation and high perforin content. Correlation was observed between in vitro recombinase activity of the mutant proteins, NK cell abnormalities, and in vivo clinical phenotype. Addition of serotherapy in the conditioning regimen, with the aim of depleting the autologous NK cell compartment, may be important to facilitate engraftment and immune reconstitution in patients with RAG and NHEJ defects treated by HSCT.
Palabras clave
Natural killer cells | Recombinase-activating genes | Non-homologous end joining | Immunodeficiency | CD56 | Interferon-gamma | Degranulation
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