PT  - JOURNAL ARTICLE
AU  - Vandewalle, Christina L
AU  - Falorni, Alberto
AU  - Lernmark, Åke
AU  - Goubert, Patrick
AU  - Dorchy, Harry
AU  - Coucke, Willy
AU  - Semakula, Crispin
AU  - Van Der Auwera, Bart
AU  - Kaufman, Leon
AU  - Schuit, Frans C
AU  - Pipeleers, Daniël G
AU  - Gorus, Frans K
TI  - Associations of GAD65- and IA-2-Autoantibodies With Genetic Risk Markers in New-Onset IDDM Patients and Their Siblings. The Belgian Diabetes Registry
AID  - 10.2337/diacare.20.10.1547
DP  - 1997 Oct 01
TA  - Diabetes Care
PG  - 1547--1552
VI  - 20
IP  - 10
4099  - http://care.diabetesjournals.org/content/20/10/1547.short
4100  - http://care.diabetesjournals.org/content/20/10/1547.full
SO  - Diabetes Care1997 Oct 01; 20
AB  - 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.