title: Millennium award recipient contribution. Identification of children with early onset and high incidence of anti-islet autoantibodies.
abstract: A total of 21,000 general population newborns (NECs) and 693 young siblings-offspring of patients with type 1A diabetes (SOCs) were class II genotyped and 293 NECs and 72 SOCs with the high-risk genotype, DR3/4, DQB1*0302 have been prospectively evaluated. Seventeen individuals who converted to persistent autoantibody positivity and two autoantibody-negative control groups (35 SOCs and 24 NECs) were typed for HLA-A class I alleles. The A1, A2 genotype was significantly increased among the autoantibody-positive subjects (47%) compared to autoantibody-negative SOCs (14%, P = 0.01) and NECs (13%, P = 0.02). Life-table analysis of DR3/4, DQB1*0302 siblings revealed a risk of 75% for development of islet autoantibodies by the age of 2 years for those with A1, A2. The HLA-A2 phenotype frequency was increased among an independent DR3/4, DQB1*0302 young diabetes cohort (64% versus 33% for autoantibody-negative NECs). These results suggest that a high incidence and early appearance of islet autoantibodies for siblings of patients with type 1A diabetes are associated with DR3/4, DQB1*0302 and potentially increased with HLA-A genotype A1, A2.
authors.affiliation: Barbara Davis Center, Department of Immunology, University of Colorado, Denver, Colorado 80262, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Robles
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Tianbao
authors.initials: T
authors.lastname: Wang
authors.forename: Henry A
authors.initials: HA
authors.lastname: Erlich
authors.forename: Teodorica L
authors.initials: TL
authors.lastname: Bugawan
authors.forename: Sunanda R
authors.initials: SR
authors.lastname: Babu
authors.forename: Kathy
authors.initials: K
authors.lastname: Barriga
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
authors.forename: Michelle
authors.initials: M
authors.lastname: Hoffman
authors.forename: Georgeanna
authors.initials: G
authors.lastname: Klingensmith
authors.forename: Liping
authors.initials: L
authors.lastname: Yu
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000483:Alleles; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D015803:HLA-DR3 Antigen / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007223:Infant; D007328:Insulin / Q000235:genetics* / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D011446:Prospective Studies
chemical_list: D001323:Autoantibodies; D015234:HLA-A Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007328:Insulin