Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells

Gao, Yifang, Workman, Sarita, Gadola, Stephan, Elliott, Tim, Grimbacher, Bodo and Williams, Anthony (2014) Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells. Journal of Allergy and Clinical Immunology, 133 (5), 1420-1428.e1. (doi:10.1016/j.jaci.2013.10.059). (PMID:24582167)

Abstract

Background Common 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. Objective An evaluation of the function and number of iNKT cells in CVID. Methods Six-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. Results A reduction in the number of iNKT cells (31 iNKT cells/105 T cells) in patients with CVID compared with healthy controls (100 iNKT cells/105 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. Conclusion iNKT cells are deficient and/or functionally impaired in most of the patients with CVID.

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Contributors

Author: Tim Elliott

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