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Inborn errors of the development of human natural killer cells

Jouanguy, Emmanuelle; Gineau, Laure; Cottineau, Julien; Béziat, Vivien; Vivier, Eric; Casanova, Jean-Laurent

Current Opinion in Allergy & Clinical Immunology: December 2013 - Volume 13 - Issue 6 - p 589–595
doi: 10.1097/ACI.0000000000000011
PRIMARY IMMUNE DEFICIENCY DISEASE: Edited by Ramsay L. Fuleihan and Bruce D. Mazer

Purpose of review: Inborn errors of human natural killer (NK) cells may affect the development of these cells, their function, or both. There are two broad categories of genetic defects of NK cell development, depending on whether the deficiency is apparently specific to NK cells or clearly affects multiple hematopoietic lineages. We review here recent progress in the genetic dissection of these NK deficiencies (NKDs).

Recent findings: Patients with severe combined immunodeficiencies bearing mutations of adenosine deaminase, adenylate kinase 2, interleukin-2 receptor gamma chain, and Janus kinase 3 genes present NKDs and are prone to a broad range of infections. Patients with GATA binding protein 2 deficiency are susceptible to both mycobacterial and viral infections, and display NKDs and a lack of monocytes. Rare patients with mini chromosomal maintenance 4 deficiency display an apparently selective NKD associated with viral infections, but they also display various nonhematopoietic phenotypes, including adrenal insufficiency and growth retardation.

Summary: These studies have initiated a genetic dissection of the development of human NK cells. Further studies are warranted, including the search for genetic causes of NKD in particular. This research may lead to the discovery of molecules specifically controlling the development of NK cells and to improvements in our understanding of the hitherto elusive function of these cells in humans.

aLaboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Hospital for Sick Children

bParis Descartes University, Imagine Institute, Paris, France

cSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, USA

dCenter for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden

eCentre d’Immunologie de Marseille-Luminy, INSERM U1104


gAix Marseille Université, UM2

hService d’Immunologie, Assistance Publique – Hôpitaux de Marseille, Hôpital de la Conception, Marseille

iPediatric Hematology-Immunology Unit, Necker Hospital, Paris, France

Correspondence to Emmanuelle Jouanguy, Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980 and University Paris Descartes, Necker Hospital, 149 rue de Sèvres, 75015 Paris, France. Tel: +33 1 72 60 65 28; e-mail:

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