An increased frequency of NK cell receptor and HLA-C group 1 combinations in early-onset type 1 diabetes.
Diabetologia
; 54(12): 3062-70, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-21909837
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antígenos HLA-C
/
Diabetes Mellitus Tipo 1
/
Receptores de Células Matadoras Naturais
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adolescent
/
Child
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Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Diabetologia
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido