Persistence of natural killer cells with expansion of a hypofunctional CD56− CD16+ KIR+ NKG2C+ subset in a patient with atypical Janus kinase 3–deficient severe combined immunodeficiency

• Published in: Journal of allergy and clinical immunology 2013-04, Vol.131 (4), p.1230-1233.e2
• Main Authors: Farnault, Laure, MD, Chambost, Hervé, MD, Michel, Gérard, MD, Thuret, Isabelle, MD, de Saint Basile, Geneviève, MD, Fischer, Alain, MD, PhD, Picard, Capucine, MD, PhD, Picard, Christophe, MD, Orlanducci, Florence, Farnarier, Catherine, MD, Moretta, Alessandro, MD, PhD, Olive, Daniel, MD, PhD
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Antigens; Antigens, CD56; B-Lymphocytes; B-Lymphocytes - immunology; Biological and medical sciences; CD56 Antigen - genetics; CD56 Antigen - immunology; Child, Preschool; Consanguinity; Cytomegalovirus; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Hematology; Human health and pathology; Humans; Immune system; Immunopathology; Janus Kinase 3; Janus Kinase 3 - deficiency; Janus Kinase 3 - genetics; Janus Kinase 3 - immunology; Killer Cells, Natural; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Life Sciences; Lymphocytes; Male; Medical sciences; Mortality; Mutation; NK Cell Lectin-Like Receptor Subfamily C; NK Cell Lectin-Like Receptor Subfamily C - genetics; NK Cell Lectin-Like Receptor Subfamily C - immunology; Receptors, IgG; Receptors, IgG - genetics; Receptors, IgG - immunology; Receptors, KIR; Receptors, KIR - genetics; Receptors, KIR - immunology; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Severe Combined Immunodeficiency; Severe Combined Immunodeficiency - genetics; Severe Combined Immunodeficiency - immunology; Severe Combined Immunodeficiency - pathology; T-Lymphocytes; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Viral infections
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2012.08.047

[...]little is known about the mechanisms by which homozygous JAK3 R117C missense mutations impair JAK3 signaling in lymphocyte ontogeny to result in the persistence of dysfunctional NK cells, although a hypomorphic mutation could be possible. [...]the present study describes a case of T-B+NK+ SCID caused by a homozygous JAK3 missense mutation, resulting in leaky SCID.