Associations of GAD65- and IA-2-autoantibodies with genetic risk markers in new-onset IDDM patients and their siblings: The Belgian Diabetes Registry

Research output: Contribution to journalArticle


OBJECTIVE - To investigate the association of GAD (65-kDa) autoantibodies (GAD65-Abs) and IA-2 autoantibodies (IA-2-Abs) with human leukocyte antigen (HLA)-DQ and insulin gene (INS) risk markers in patients with recent-onset IDDM and their siblings. RESEARCH DESIGN AND METHODS - Blood was sampled from 608 recent-onset IDDM patients and 480 siblings, aged 0-39 years and consecutively recruited by the Belgian Diabetes Registry, to determine GAD65- and IA-2-Ab (radiobinding assay), HLA-DQ- (allele-specific oligonucleotyping), and INS-genotypes (restriction fragment length polymorphism analysis; siblings, n = 439). RESULTS - At the onset of IDDM, GAD65-Abs were preferentially associated with two populations at genetic risk but only in the 20- to 39-year age-group: 1) their prevalence was higher in carriers of DQA1 *0301-DQB1 *0302 (88 vs. 73% in non[DQA1 *0301-DQB1 *0302], P = 0.001), and 2) an association was found in patients lacking this haplotype but carrying DQA1 *0501-DQB1 *0201, together with INS I/I (87 vs. 54% vs. non[INS I/I], P = 0.003). Siblings of IDDM patients also presented the association of GAD65-Abs with DQA1*0301-DQB1*0302 (13 vs. 2% non[DQA1 *0301 -DQB1 *0302], P < 0.001), while associations with the second genetic risk group could not yet be assessed. At the onset of IDDM, IA-2-Ab prevalence was higher in carriers of DQA1 *0301-DQB1*0302 (69 vs. 39% non[DQA1 *0301-DQB1 *0302], P < 0.001) but not of DQA1 *0501-DQB1*0201 or INS I/I. This association was present in both the 0- to 19- and the 20- to 39-year age-groups. It was also found in siblings of IDDM patients (4 vs. 0% non[DQA1 *0301-DQB1 *0302], P < 0.001). CONCLUSIONS - Both GAD65- and IA- 2-Abs exhibit higher prevalences in presence of HLA-DQ- and/or INS-genetic risk markers. Their respective associations differ with age at clinical onset, suggesting a possible usefulness in the identification of subgroups in this heterogeneous disease.


  • Christina L. Vandewalle
  • Alberto Falorni
  • Åke Lernmark
  • Patrick Goubert
  • Harry Dorchy
  • Willy Coucke
  • Crispin Semakula
  • Bart Van Der Auwera
  • Leon Kaufman
  • Frans C. Schuit
  • Daniël G. Pipeleers
  • Frans K. Gorus
External organisations
  • University of Washington
  • Vrije Universiteit Brussel (VUB)
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)1547-1552
JournalDiabetes Care
Issue number10
Publication statusPublished - 1997 Jan 1
Publication categoryResearch
Externally publishedYes