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oai:repisalud.isciii.es:20.500.12105/204422024-11-29T00:28:38Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967
Repisalud author Dobbs, Kerry author Tabellini, Giovanna author Calzoni, Enrica author Patrizi, Ornella author Martinez, Paula author Giliani, Silvia Clara author Moratto, Daniele author Al-Herz, Waleed author Cancrini, Caterina author Cowan, Morton author Bleesing, Jacob author Booth, Claire author Buchbinder, David author Burns, Siobhan O. author Chatila, Talal A. author Chou, Janet author Daza-Cajigal, VanessaAutor/a del sistema sanitario público de las Islas Baleares Orcid author de Bruin, Lisa M. Ott author de la Morena, MaiteTeresa author Di Matteo, Gigliola author Finocchi, Andrea author Geha, Raif author Goyal, Rakesh K. author Hayward, Anthony author Holland, Steven author Huang, Chiung-Hui author Kanariou, Maria G. author King, Alejandra author Kaplan, Blanka author Kleva, Anastasiya author Kuijpers, Taco W. author Lee, Bee Wah author Lougaris, Vassilios author Massaad, Michel author Meyts, Isabelle author Morsheimer, Megan author Neven, Benedicte author Pai, Sung-Yun author Plebani, Alessandro author Prockop, Susan author Reisli, Ismail author Soh, Jian Yi author Somech, Raz author Torgerson, Troy R. author Kim, Yae-Jaen author Walter, Jolan E. author Gennery, Andrew R. author Keles, Sevgi author Manis, John P. author Marcenaro, Emanuela author Moretta, Alessandro author Parolini, Silvia author Notarangelo, Luigi D 2024-07-11T09:10:37Z 2024-07-11T09:10:37Z 2017-07-17 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. 10.3389/fimmu.2017.00798 1664-3224 Frontiers in Immunology http://hdl.handle.net/20.500.13003/9743 28769923 L617387078 2-s2.0-85025431730 http://hdl.handle.net/20.500.12105/20442 405547800001 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. eng Natural killer cells Recombinase-activating genes Non-homologous end joining Immunodeficiency CD56 Interferon-gamma Degranulation 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 research article