Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Åke Lernmark

Principal investigator

Default user image.

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

Author

  • 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

Summary, in English

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.

Publishing year

1997-01-01

Language

English

Pages

1547-1552

Publication/Series

Diabetes Care

Volume

20

Issue

10

Document type

Journal article

Publisher

American Diabetes Association

Topic

  • Endocrinology and Diabetes

Status

Published

ISBN/ISSN/Other

  • ISSN: 0149-5992