An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes

Mehers, K. L., Long, A. E., Slik, A. R., Aitken, R. J., Nathwani, V., Wong, Florence Susan ORCID: https://orcid.org/0000-0002-2812-8845, Bain, S., Gill, G., Roep, B. O., Bingley, P. J. and Gillespie, K. 2011. An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes. Diabetologia 54 (12) , pp. 3062-3070. 10.1007/s00125-011-2299-x

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Abstract

Aims/hypothesis Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptor (KIR) genes and their HLA class I ligands. Alterations in NK cell activity have been associated with type 1 diabetes. The aim of this study was to determine whether KIR–HLA class I gene frequency: (1) is altered in a current population with type 1 diabetes compared with healthy controls; and (2) has changed over the half century in which the incidence of type 1 diabetes has increased rapidly. Methods KIR–HLA class I gene frequencies were compared in 551 individuals diagnosed with type 1 diabetes ≤15 years of age (394 in a current cohort and 157 from the historical ‘Golden Years’ cohort) and 168 healthy controls. The overall balance of activation and inhibition was analysed using KIR–HLA genotype models. Results Children with type 1 diabetes who were positive for KIR2DS2/KIR2DL2 and KIR2DL3 were more often homozygous for HLA-C group 1 and this effect was strongest in children diagnosed with diabetes before the age of 5 years (p = 0.003, corrected p [p corr] = 0.012) and (p = 0.001, p corr = 0.004), respectively. Children with type 1 diabetes have fewer inhibitory KIRs with their corresponding ligands compared with healthy controls (p = 1.9 × 10−4). This pattern of NK activation has not changed significantly in individuals with type 1 diabetes over the last half century. Conclusions/interpretation Activating combinations of KIR–HLA genes are more frequent in young children with type 1 diabetes diagnosed in the first 5 years of life, suggesting that NK cell responses may be altered in this group.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	human leucocyte antigen, killer immunoglobulin-like receptor, natural killer cell, type 1 diabetes
Publisher:	Springer
ISSN:	0012-186X
Last Modified:	19 Oct 2022 10:02
URI:	https://orca.cardiff.ac.uk/id/eprint/23032

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