Lp. Yu et al., DRB1*04 and DQ alleles: Expression of 21-hydroxylase autoantibodies and risk of progression to Addison's disease, J CLIN END, 84(1), 1999, pp. 328-335
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 hete
rozygous 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 p
resent in 14 of 21 patients with Addison's disease (8 of 12 with diabetes a
nd 6 of 9 without diabetes or antiislet autoantibodies) us. 0.7% of the gen
eral population (109 of 15,547; P < 10(-6)) and 11% of patients with DM wit
hout Addison's disease (62 of 578; P < 10(-6)). Among patients with diabete
s with DQ8, Addison's disease was strongly associated with the specific DRB
1 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 D
RB1*0404; P < 0.001). Among 21-hydroxylase autoantibody-positive DQ8 patien
ts, 80% with DRB1*0404 (12 of 15) had Addison's disease, in contrast to 1 o
f 10 autoantibody-positive patients with DRB1*0401 or DRB1*0402 (P < 0.001)
. We conclude that patients with DRB1*0404 and 21-hydroxylase autoantibodie
s 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 presenc
e of 21-hydroxylase autoantibodies.