title: An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes.
abstract: OBJECTIVE
  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
  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: Diabetes and Metabolism, Learning and Research, University of Bristol, Southmead Hospital, Bristol, UK.
authors: K L
authors: KL
authors: Mehers
authors: A E
authors: AE
authors: Long
authors: A R
authors: AR
authors: van der Slik
authors: R J
authors: RJ
authors: Aitken
authors: V
authors: V
authors: Nathwani
authors: F S
authors: FS
authors: Wong
authors: S
authors: S
authors: Bain
authors: G
authors: G
authors: Gill
authors: B O
authors: BO
authors: Roep
authors: P J
authors: PJ
authors: Bingley
authors: K M
authors: KM
authors: Gillespie
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000276:immunology; D015236:HLA-C Antigens / Q000235:genetics* / Q000276:immunology*; D006720:Homozygote; D006801:Humans; D007223:Infant; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D055607:Receptors, Natural Killer Cell / Q000235:genetics* / Q000276:immunology*
chemical_list: D015236:HLA-C Antigens; D055607:Receptors, Natural Killer Cell