Insulin autoantibodies and high titre islet cell antibodies are preferentially associated with the HLA DQA1*0301-DQB1*0302 haplotype at clinical type 1 (insulin-dependent) diabetes mellitus before age 10 years, but not at onset between age 10 and 40 years. The Belgian Diabetes Registry.
Demographic and biological data were collected from all Caucasian Type 1 diabetic patients (n = 279) who were recruited at clinical onset by the Belgian Diabetes Registry over 34 months. The male/female ratio was significantly higher for onset between age 20 and 40 years (2.4) than before age 20 years (1.0); no age-or sex-differences were noticed in serum fructosamine concentration. Total and high concentrations of insulin autoantibodies and islet cell antibodies were preferentially associated with the HLA DQA1*0301-DQB1*0302 susceptibility haplotype. The occurrence of both types of antibodies was also correlated, irrespective of haplotype. At onset before age 10 years, the high risk genotype DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 was more prevalent than all other DQA1-DQB1 genotypes taken together, leading to a higher prevalence of the DQA1*0301-DQB1*0302 haplotype in this age group (75%) than in the 10-39 years age group (54%). Under age 10 years, the presence of DQA1*0301-DQB1*0302 was strongly associated with insulin autoantibodies (90%) and islet cell autoantibodies (92% with 85% of high titre), whereas patients without this haplotype were less frequently positive for insulin autoantibodies (31%) or islet cell autoantibodies (38% high titre). In the group with onset at age 10-39 years, the DQA1*0301-DQB1*0302 haplotype presented a lower association with insulin autoantibodies (approximately 40%) and islet cell autoantibodies (50 to 65% high titre), prevalences which no longer differed from those in subjects lacking this haplotype.(ABSTRACT TRUNCATED AT 250 WORDS)
Vandewalle
C L
CL
Diabetes Research Centre, Vrije Universiteit Brussel, Belgium.
Decraene
T
T
Schuit
F C
FC
De Leeuw
I H
IH
Pipeleers
D G
DG
Gorus
F K
FK
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D005260:Female; D019270:Fructosamine; D005838:Genotype; D006683:HLA-DQ Antigens / Q000097:blood / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006239:Haplotypes; D006595:Hexosamines / Q000097:blood; D006801:Humans; D007330:Insulin Antibodies / Q000097:blood*; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male
D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006595:Hexosamines; D007330:Insulin Antibodies; C024211:islet cell antibody; D019270:Fructosamine