DRB104 and DQ alleles : Expression of 21-hydroxylase autoantibodies and risk of progression to Addison's disease

• Published in: The journal of clinical endocrinology and metabolism 1999, Vol.84 (1), p.328-335
• Main Authors: LIPING YU, BREWER, K. W, REWERS, M. J, EISENBARTH, G. S, GATES, S, ANYA WU, TIANBAO WANG, BABU, S. R, GOTTLIEB, P. A, FREED, B. M, NOBLE, J, ERLICH, H. A
• Format: Article
• Language: English
• Subjects: Addison Disease - etiology; Addison Disease - genetics; Adolescent; Adult; Alleles; Associated diseases and complications; Autoantibodies - blood; Biological and medical sciences; Child; Child, Preschool; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; HLA-DQ Antigens - genetics; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Infant; Medical sciences; Middle Aged; Risk; Steroid 21-Hydroxylase - immunology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.84.1.328

Of 957 patients with type 1 diabetes without known Addison's disease 1.6% (n = 15) were positive for 21-hydroxylase autoantibodies. Among DQ8/DQ2 heterozygous patients, the percentage expressing 21-hydroxylase autoantibodies was 5% (10 of 208) vs. less than 0.5% of patients with neither DQ8 nor DQ2. Three of the diabetic patients found to have 21-hydroxylase autoantibodies on screening were subsequently diagnosed with Addison's disease. Overall, the genotype DQ8/DQ2, consisting of DRB1*0404/DQ8 with DRB1*0301/DQ2, was present in 14 of 21 patients with Addison's disease (8 of 12 with diabetes and 6 of 9 without diabetes or antiislet autoantibodies) vs. 0.7% of the general population (109 of 15,547; P < 10(-6)) and 11% of patients with DM without Addison's disease (62 of 578; P < 10(-6)). Among patients with diabetes with DQ8, Addison's disease was strongly associated with the specific DRB1 subtype, DRB1*0404 (8 of 9 patients from 8 families, in contrast to only 109 of 408 DQ8 DM patients with diabetes without Addison's disease having DRB1*0404; P < 0.001). Among 21-hydroxylase autoantibody-positive DQ8 patients, 80% with DRB1*0404 (12 of 15) had Addison's disease, in contrast to 1 of 10 autoantibody-positive patients with DRB1*0401 or DRB1*0402 (P < 0.001). We conclude that patients with DRB1*0404 and 21-hydroxylase autoantibodies are at high risk for Addison's disease. Patients with DRB1*0401 and DRB1*0402 have more limited progression to Addison's disease despite the presence of 21-hydroxylase autoantibodies.