Autoimmune and clinical characteristics of type I diabetes in children with different genetic risk loads defined by HLA-DQB1 alleles. Childhood Diabetes in Finland Study Group.
1. The impact of different genetic risk loads defined by HLA-DQB1 alleles on the autoimmune and clinical characteristics of 647 children and adolescents with recent-onset Type I diabetes was evaluated in a prospective population-based study. The subjects were divided into four groups based on HLA-DQB1 genotypes: DQB1*0302/0201 (high risk), *0302/x (moderate risk), *0201/y (low risk) and *z/z (decreased risk). 2. Close to two thirds (62.3%) of the subjects possessed a high or moderate risk genotype. A decreased frequency of positivity for islet cell antibodies (ICA) and insulin autoantibodies (IAA) (76.8% compared with 85.3%; P = 0.05, and 30.5% compared with 50.8%, P = 0.0006, respectively) but not of positivity for antibodies to the 65 kDa isoform of glutamate decarboxylase was observed in children with the DQB1*0201/y genotype compared with other children. Among ICA-negative subjects, those with the DQB1*0201/y genotype had higher serum C-peptide levels over the first 2 years after the diagnosis of Type I diabetes than those with other genotypes (P = 0.028). 3. Our data provide some evidence of HLA-DQB1-determined heterogeneity in the autoimmune and clinical characteristics of childhood Type I diabetes at the time of the clinical manifestation. This suggests differences between children with various HLA-DQB1 genotypes in the pace and/or intensity of the beta-cell destructive process leading to clinical Type I diabetes.
Komulainen
J
J
Department of Pediatrics, Kuopio University Hospital, Finland.
Knip
M
M
Sabbah
E
E
Vähäsalo
P
P
Lounamaa
R
R
Akerblom
H K
HK
Reijonen
H
H
Ilonen
J
J
D000293:Adolescent; D000483:Alleles; D001323:Autoantibodies / Q000097:blood*; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D004198:Disease Susceptibility; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007330:Insulin Antibodies / Q000097:blood; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D011446:Prospective Studies
D001323:Autoantibodies; D002096:C-Peptide; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D007330:Insulin Antibodies; C024211:islet cell antibody; D005968:Glutamate Decarboxylase