Pteridin-dependent hydroxylases as autoantigens in autoimmune polyendocrine syndrome type I.
Autoimmune polyendocrine syndrome type I (APS I) is characterized by autoantibodies, often directed towards tissue-specific enzymes in the affected organs. We have earlier reported the identification of tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) as autoantigens in APS I associated with intestinal dysfunction and alopecia, respectively. These two enzymes, together with phenylalanine hydroxylase (PAH), constitute the group of biopterin-dependent hydroxylases, which all are involved in the biosynthesis of neurotransmitters. A clone encoding PAH was used for in vitro transcription/translation, followed by immunoprecipitation with sera from 94 APS I patients and 70 healthy controls. Of the APS I patients, 25% had PAH antibodies, and no reactivity was detected in the controls. No association with the main clinical components of APS I was found with PAH antibodies. Altogether, 59 sera from the 94 APS I patients reacted with at least one of TPH, TH, or PAH, whereas 35 showed no reactivity. Nineteen of the sera contained antibodies towards all enzymes, 12 to TPH only and 12 to TH only. No sera showed antibodies that reacted to only PAH. An immunocompetition assay demonstrated that the reactivity against PAH represents a cross-reactivity with TPH, whereas antibodies against TPH and TH are directed towards epitopes unique for the two enzymes.
Ekwall
O
O
Department of Medical Sciences, University Hospital, Uppsala University, Sweden. olov.ekwall@medsci.uu.se
Hedstrand
H
H
Haavik
J
J
Perheentupa
J
J
Betterle
C
C
Gustafsson
J
J
Husebye
E
E
Rorsman
F
F
Kämpe
O
O
D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000737:chemistry / Q000276:immunology; D020134:Catalytic Domain; D005387:Finland; D006801:Humans; D007558:Italy; D008958:Models, Molecular; D009664:Norway; D010651:Phenylalanine Hydroxylase / Q000737:chemistry / Q000276:immunology*; D016884:Polyendocrinopathies, Autoimmune / Q000201:enzymology / Q000276:immunology*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012016:Reference Values; D013548:Sweden; D014365:Tryptophan Hydroxylase / Q000737:chemistry / Q000276:immunology; D014446:Tyrosine 3-Monooxygenase / Q000737:chemistry / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D010651:Phenylalanine Hydroxylase; D014446:Tyrosine 3-Monooxygenase; D014365:Tryptophan Hydroxylase