Stage 1 (increased plasma renin) for patients with APS-1 and Stage 2 (no response of cortisol to ACTH-test) for patients with APS-2/APS-4 were established as the points of no return in the progression to AAD.
APS2, which occurs at a much higher frequency, is classically defined as the coexistence of autoimmune Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes.
We determined the HLA-DR and HLA-DQA1 association in 112 unrelated patients with APS II (n = 29), APS III (n = 83) and 184 unrelated patients with single-component diseases without further manifestations of APS: Graves' disease (n = 70), Hashimoto's thyroiditis (n = 53), autoimmune Addison's disease (n = 15), vitiligo (n = 16) and alopecia (n = 30), and 72 healthy controls - German Caucasians - to identify possible predisposing and protective HLA class II alleles in APS.
There was an association of the G allele at CTLA-4A/G in AAD subjects (P = 0.008 vs. controls), which was stronger in subjects with AAD as a component of APS2 than in subjects with isolated AAD.