Mapping of human autoantibody epitopes on aromatic L-amino acid decarboxylase.

Abstract

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, 124 with type 1 diabetes mellitus, 36 with Graves' disease, and 141 healthy control subjects, and we evaluated the autoantibody-mediated enzymatic inhibition.

RESULTS:

AADC antibodies (Ab) were detected in 12 of 18 (67%) APS I patients and in six of 199 (3%) autoimmune Addison's disease patients. Four patients with autoimmune hepatitis were all positive for AADCAb. None of the 141 healthy control subjects, 82 patients with nonautoimmune adrenal insufficiency, 124 with type 1 diabetes mellitus, and 36 with Graves' disease were 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 seven of 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.

• Authors: Paola Candeloro, Carla Borri Voltattorni, Roberto Perniola, Mariarita Bertoldi, Corrado Betterle, Massimo Mannelli, Roberta Giordano, Annamaria De Bellis, Claudio Tiberti, Stefano Laureti, Fausto Santeusanio, Alberto Falorni
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 92 Issue 3 Pg. 1096-105 (Mar 2007) ISSN: 0021-972X [Print] United States
• PMID: 17200166 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Aromatic-L-Amino-Acid Decarboxylases

Topics

• Adolescent
• Adult
• Aged
• Animals
• Aromatic-L-Amino-Acid Decarboxylases (chemistry, immunology, metabolism)
• Autoantibodies (blood, chemistry, metabolism)
• Autoimmune Diseases (blood, immunology)
• Base Sequence
• Child
• Child, Preschool
• Epitope Mapping
• Female
• Humans
• Infant
• Male
• Middle Aged
• Sus scrofa