Yu L, Brewer K W, Gates S, Wu A, Wang T, Babu S R, Gottlieb P A, Freed B M, Noble J, Erlich H A, Rewers M J, Eisenbarth G S
Barbara Davis Center for Childhood Diabetes, University of Colorado, Denver 80262, USA.
J Clin Endocrinol Metab. 1999 Jan;84(1):328-35. doi: 10.1210/jcem.84.1.5414.
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 DRB10404/DQ8 with DRB10301/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, DRB10404 (8 of 9 patients from 8 families, in contrast to only 109 of 408 DQ8 DM patients with diabetes without Addison's disease having DRB10404; P < 0.001). Among 21-hydroxylase autoantibody-positive DQ8 patients, 80% with DRB10404 (12 of 15) had Addison's disease, in contrast to 1 of 10 autoantibody-positive patients with DRB10401 or DRB10402 (P < 0.001). We conclude that patients with DRB10404 and 21-hydroxylase autoantibodies are at high risk for Addison's disease. Patients with DRB10401 and DRB10402 have more limited progression to Addison's disease despite the presence of 21-hydroxylase autoantibodies.
在957例无已知艾迪生病的1型糖尿病患者中，1.6%（n = 15）的患者21-羟化酶自身抗体呈阳性。在DQ8/DQ2杂合子患者中，表达21-羟化酶自身抗体的百分比为5%（208例中的10例），而既无DQ8也无DQ2的患者中这一比例不到0.5%。筛查发现有21-羟化酶自身抗体的3例糖尿病患者随后被诊断为艾迪生病。总体而言，由DRB10404/DQ8与DRB10301/DQ2组成的DQ8/DQ2基因型在21例艾迪生病患者中的14例中出现（12例糖尿病患者中的8例以及9例无糖尿病或抗胰岛自身抗体的患者中的6例），而在普通人群中为0.7%（15547例中的109例；P < 10^(-6)），在无艾迪生病的糖尿病患者中为11%（578例中的62例；P < 10^(-6)）。在有DQ8的糖尿病患者中，艾迪生病与特定的DRB1亚型DRB10404密切相关（8个家族的9例患者中的8例，相比之下，408例无艾迪生病的DQ8糖尿病患者中只有109例具有DRB10404；P < 0.001）。在21-羟化酶自身抗体阳性的DQ8患者中，80%具有DRB10404（15例中的12例）患有艾迪生病，而具有DRB10401或DRB10402的10例自身抗体阳性患者中有1例患有艾迪生病（P < 0.001）。我们得出结论，具有DRB10404和21-羟化酶自身抗体的患者患艾迪生病的风险很高。尽管存在21-羟化酶自身抗体，但具有DRB10401和DRB10402的患者发展为艾迪生病的进程较为有限。
