Context: Aromatic l-amino acid decarboxylase (AADC) is target of autoantibodies in autoimmune polyendocrine syndrome I (APS I), especially in patients with autoimmune hepatitis. Little information is currently available on AADC autoantibody epitopes and on the interrelation between autoantibody-mediated inhibition of enzymatic activity and epitope specificity.

Design: We tested the immunoreactivity of full-length porcine AADC and of eight fragments of the enzyme with human serum from 18 patients with APS I, 199 with non-APS I autoimmune Addison's disease (AAD), 124 with type 1 diabetes mellitus (T1DM), 36 with Graves' disease (GD) and 141 healthy control subjects (HS) and we evaluated the autoantibody-mediated enzymatic inhibition.

Results: AADCAb were detected in 12/18 (67%) APS I and in 6/199 (3%) AAD. Four patients with autoimmune hepatitis were all positive for AADCAb. None of 141 HS, 82 patients with non-autoimmune adrenal insufficiency, 124 with T1DM and 36 with GD was found positive. Two epitope regions, corresponding to amino acids 274-299 (E1) and 380-471 (E2) were identified. Localization of E1 was confirmed by displacement studies with synthetic peptides corresponding to peptides of porcine AADC. All 12 AADCAb-positive APS I sera reacted with E1 and 7/12 (58%) reacted also with E2. E2-specific, but not E1-specific, autoantibodies were associated with a significant inhibition of in vitro AADC enzymatic activity.

Conclusions: We mapped the human AADCAb epitopes to the middle and COOH-terminal regions of the enzyme. Autoantibodies to the COOH-terminal region induce a significant inhibition of enzymatic activity.