Toggle Main Menu Toggle Search

Open Access padlockePrints

Natural killer cells from patients with recombinase-activating gene and non-homologous end joining gene defects comprise a higher frequency of CD56bright NKG2A+++ cells, and yet display increased degranulation and higher perforin content

Lookup NU author(s): Professor Andrew GenneryORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2017 Dobbs, Tabellini, Calzoni, Patrizi, Martinez, et al. 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 CD56bright 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.

Publication metadata

Author(s): Dobbs K, Tabellini G, Calzoni E, Patrizi O, Martinez P, Giliani SC, Moratto D, Al-Herz W, Cancrini C, Cowan M, Bleesing J, Booth C, Buchbinder D, Burns SO, Chatila TA, Chou J, Daza-Cajigal V, de Bruin LMO, de la Morena M, Di Matteo G, Finocchi A, Geha R, Goyal RK, Hayward A, Holland S, Huang C-H, Kanariou MG, King A, Kaplan B, Kleva A, Kuijpers TW, Lee BW, Lougaris V, Massaad M, Meyts I, Morsheimer M, Neven B, Pai S-Y, Plebani A, Prockop S, Reisli I, Soh JY, Somech R, Torgerson TR, Kim Y-J, Walter JE, Gennery AR, Keles S, Manis JP, Marcenaro E, Moretta A, Parolini S, Notarangelo LD

Publication type: Article

Publication status: Published

Journal: Frontiers in Immunology

Year: 2017

Volume: 8

Online publication date: 17/07/2017

Acceptance date: 23/06/2017

Date deposited: 01/11/2017

ISSN (print): 1664-3224

Publisher: Frontiers Media S.A.


DOI: 10.3389/fimmu.2017.00798


Altmetrics provided by Altmetric