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An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes.
MedLine Citation:
PMID:  21909837     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
K L Mehers; A E Long; A R van der Slik; R J Aitken; V Nathwani; F S Wong; S Bain; G Gill; B O Roep; P J Bingley; K M Gillespie
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-9-10
Journal Detail:
Title:  Diabetologia     Volume:  -     ISSN:  1432-0428     ISO Abbreviation:  -     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-9-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Diabetes and Metabolism, Learning and Research, University of Bristol, Southmead Hospital, Bristol, UK.
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