title: Progression to type 1 diabetes and autoantibody positivity in relation to HLA-risk genotypes in children participating in the ABIS study.
abstract: BACKGROUND
  Autoantibodies against beta-cell antigens together with human leukocyte antigen (HLA)-risk genotypes are used as predictive markers for type 1 diabetes (T1D). In this study, we have investigated the role of HLA-risk and -protective genotypes for development of beta-cell autoantibodies and progression to T1D in healthy children.
  
  
  METHODS
  T1D-related HLA genotypes and autoantibodies against glutamic acid decarboxylase [glutamic acid decarboxylase antibodies (GADA)] and islet antigen-2 (IA-2A) were studied at 1, 2.5 and 5 yr of age in unselected healthy children and children with T1D participating in the All Babies In Southeast Sweden (ABIS) study.
  
  
  RESULTS
  GADA or IA-2A positivity at 5 yr of age was associated with DR4-DQ8 haplotype and DR3-DQ2/DR4-DQ8 genotype. By the age of 6-7 yr, we identified 32 children with T1D among the 17 055 participants in the ABIS study. Eight of 2329 (0.3%) non-diabetic children had permanent autoantibodies, and 143 of 2329 (6%) children had transient autoantibodies. HLA-risk genotypes associated with T1D, whereas protective genotypes were seldom found in children with T1D. Children with permanent autoantibodies had more often risk-associated DR4-DQ8 haplotype than autoantibody-negative children. No associations with HLA-risk or -protective genotypes were found for transient autoantibodies.
  
  
  CONCLUSIONS
  The strong relation between HLA-risk alleles and T1D once again confirmed that HLA-risk genotypes play an important role for development of T1D. However, HLA genotypes seem not to explain induction of autoantibodies, especially transient autoantibodies, in the general population, emphasizing the role of environmental factors in the initiation of autoimmunity. It seems that HLA-risk genotypes are responsible for maturation of the permanent autoantibody response.
authors.affiliation: Division of Pediatrics and Diabetes Research Centre, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. camgu@imk.liu.se
authors.forename: Camilla
authors.initials: C
authors.lastname: Gullstrand
authors.forename: Jeanette
authors.initials: J
authors.lastname: Wahlberg
authors.forename: Jorma
authors.initials: J
authors.lastname: Ilonen
authors.forename: Outi
authors.initials: O
authors.lastname: Vaarala
authors.forename: Johnny
authors.initials: J
authors.lastname: Ludvigsson
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics / Q000276:immunology*; D018450:Disease Progression; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000276:immunology; D006680:HLA Antigens / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D015994:Incidence; D018570:Risk Assessment; D013548:Sweden / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens; D006681:HLA-D Antigens; D005968:Glutamate Decarboxylase