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BackgroundCommon variable immunodeficiency (CVID) is the commonest symptomatic primary antibody disorder, with monogenic causes identified in less than 10% of all cases. X-linked proliferative disease is a monogenic disorder that is associated with hypogammaglobulinemia and characterized by a deficiency of invariant NKT (iNKT) cells. We sought to evaluate whether a defect in iNKT cell number or function was associated with CVID.ObjectiveAn evaluation of the function and number of iNKT cells in CVID.MethodsSix-color flow cytometry enumerated iNKT cells in 36 patients with CVID and 50 healthy controls. Their proliferative capacity and cytokine production (IFN-γ, IL-13, IL-17) was then investigated following activation with CD1d ligand alpha-galactosylceramide.ResultsA reduction in the number of iNKT cells (31 iNKT cells/10(5) T cells) in patients with CVID compared with healthy controls (100 iNKT cells/10(5) T cells) was observed (P < .0001). Two cohorts could be discerned within the CVID group: group 1 with an abnormal number of iNKT cells (n = 28) and group 2 with a normal number of iNKT cells (n = 8). This segregation coassociated with the proliferative capacity of iNKT cells between the 2 groups. However, differences in the function of iNKT cells were noted in group 2, in which an increase in IFN-γ (P = .0016) and a decrease in IL-17 (P = .0002) production was observed between patients with CVID and controls. Finally, a significant association was seen between the number of iNKT cells and the percentage of class-switched memory B cells and propensity to lymphoproliferation (P = .002) in patients with CVID.ConclusioniNKT cells are deficient and/or functionally impaired in most of the patients with CVID.

Original publication

DOI

10.1016/j.jaci.2013.10.059

Type

Journal article

Journal

The Journal of allergy and clinical immunology

Publication Date

05/2014

Volume

133

Pages

1420 - 1428.e1

Addresses

Faculty of Medicine, Cancer Sciences Division, University of Southampton, Southampton, United Kingdom.

Keywords

Cells, Cultured, Humans, Genetic Diseases, X-Linked, Common Variable Immunodeficiency, Cytokines, Adult, Female, Male, Natural Killer T-Cells