Autoantibodies to human tryptophan hydroxylase and aromatic L-amino acid decarboxylase.
OBJECTIVE
To assess the prevalence of autoantibodies (Abs) to tryptophan hydroxylase (TPH) and aromatic l-amino acid decarboxylase (AADC) in patients with different autoimmune diseases and to analyse their respective epitopes.


METHODS
TPH and AADC Abs were measured in an immunoprecipitation assay using (35)S-labelled full-length and fragments of TPH and AADC.


METHODS
Patients with different autoimmune adrenal diseases (n=84), non-adrenal autoimmune diseases (n=37), idiopathic vitiligo (n=8) and 56 healthy blood donors were studied.


RESULTS
Fourteen of twenty-three (61%) of patients with autoimmune polyglandular syndrome (APS) type I and 1/34 (3%) of patients with isolated Addison's disease (AD) were positive for TPH Abs. None of the patients with APS type II (n=27), coeliac disease (n=10), autoimmune thyroid disease (AITD) (n=11), type 1 diabetes mellitus (DM) (n=16) or idiopathic vitiligo (n=8) was positive for TPH Abs. AADC Abs were detected in 12/23 (52%) patients with APS type I, in 1/29 (3%) patients with APS type II and 1/34 (3%) patients with isolated AD. None of the patients with coeliac disease, type 1 DM, AITD or idiopathic vitiligo was positive for AADC Abs. TPH Abs were found to interact with the C-terminal amino acids (aa) 308-423, central aa 164-205 and N-terminal aa 1-105 of the TPH molecule. AADC Ab binding epitopes were within the C-terminal aa 382-483, the central aa 243-381 and the N-terminal aa 1-167.


CONCLUSIONS
Our study suggests that TPH Abs and AADC Abs react with several different epitopes and that different epitopes are recognized by different sera. The prevalence of TPH Abs and AADC Abs in patients with APS type I in our study is in agreement with previous reports. TPH Abs and AADC Abs were found very rarely in patients with other forms of autoimmune adrenal disease and were not detected in patients with non-adrenal autoimmune diseases.
Dal Pra
Chiara
C
FIRS Laboratories, RSR Ltd, Parc Ty Glas, Llanishen, Cardiff CF14 5DU, UK.
Chen
Shu
S
Betterle
Corrado
C
Zanchetta
Renato
R
McGrath
Vivienne
V
Furmaniak
Jadwiga
J
Rees Smith
Bernard
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001327:Autoimmune Diseases / Q000201:enzymology / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D000939:Epitopes; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments; D016884:Polyendocrinopathies, Autoimmune / Q000201:enzymology / Q000276:immunology; D011233:Precipitin Tests; D013254:Steroid 17-alpha-Hydroxylase / Q000097:blood; D013255:Steroid 21-Hydroxylase / Q000097:blood; D014365:Tryptophan Hydroxylase / Q000276:immunology*
D001323:Autoantibodies; D000939:Epitopes; D010446:Peptide Fragments; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D014365:Tryptophan Hydroxylase; D001142:Aromatic-L-Amino-Acid Decarboxylases