Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells
Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells
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.
1420-1428.e1
Gao, Yifang
eea234ba-f566-4f21-a65e-234b84cba285
Workman, Sarita
015ab902-2ad6-4b78-8064-79f7e58e785a
Gadola, Stephan
ef2fa6cf-2ccc-4fea-a7a5-cc03a9d13ab1
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Grimbacher, Bodo
76c5b722-dc7b-4df1-abd8-238f3f3652ae
Williams, Anthony
973ff46f-46f1-4d7c-b27d-0f53221e4c44
May 2014
Gao, Yifang
eea234ba-f566-4f21-a65e-234b84cba285
Workman, Sarita
015ab902-2ad6-4b78-8064-79f7e58e785a
Gadola, Stephan
ef2fa6cf-2ccc-4fea-a7a5-cc03a9d13ab1
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Grimbacher, Bodo
76c5b722-dc7b-4df1-abd8-238f3f3652ae
Williams, Anthony
973ff46f-46f1-4d7c-b27d-0f53221e4c44
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), .
(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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e-pub ahead of print date: 26 February 2014
Published date: May 2014
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 368154
URI: http://eprints.soton.ac.uk/id/eprint/368154
ISSN: 0091-6749
PURE UUID: 7afe71a6-0b13-4af6-b0ee-41af2988de49
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Date deposited: 19 Aug 2014 10:23
Last modified: 15 Mar 2024 03:08
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Contributors
Author:
Yifang Gao
Author:
Sarita Workman
Author:
Stephan Gadola
Author:
Bodo Grimbacher
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