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Pteridin-Dependent Hydroxylases as Autoantigens in Autoimmune Polyendocrine Syndrome Type I¹

Olov Ekwall, Hkan Hedstrand, Jan Haavik, Jaakko Perheentupa, Corrado Betterle, Jan Gustafsson, Eystein Husebye, Fredrik Rorsman and Olle Kämpe

Departments of Medical Sciences (O.E., H.H., F.R., O.K.) and Women’s and Children’s Health (J.G.), University Hospital, Uppsala University, SE-751 85 Uppsala, Sweden; Department of Biochemistry and Molecular Biology (J.H.) and Division of Endocrinology, Institute of Medicine (E.H.), University of Bergen, NO-5021 Bergen, Norway; the Hospital for Children and Adolescents (J.P.), University of Helsinki, FIN-00014 Helsinki, Finland; and Institute of Semeiotica Medica (C.B.), Clinical Immunology and Allergy, University of Padova, IT-35128 Padua, Italy

Address correspondence and requests for reprints to: Olov Ekwall, M.D., Department of Medical Sciences, University Hospital, Uppsala University, SE-751 85 Uppsala, Sweden. E-mail: olov.ekwall{at}medsci.uu.se

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.

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