Pteridin-dependent hydroxylases as autoantigens in autoimmune polyendocrine syndrome type I

Autoimmune polyendocrine syndrome type I(APS I) is characterized by autoant ibodies, often directed towards tissue-specific enzymes in the affected org ans. We have earlier reported the identification of tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) as autoantigens in APS I associated wit h intestinal dysfunction and alopecia, respectively. These two enzymes, tog ether with phenylalanine hydroxylase (PAH), constitute the group of biopter in-dependent hydroxylases, which all are involved in the biosynthesis of ne urotransmitters. A clone encoding PAH was used for in, vitro transcription/translation, foll owed 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 compon ents of APS I was found with PAH antibodies. Altogether, 59 sera from the 9 4 APS I patients reacted with at least one of TPH, TH, or PAH, whereas 35 s howed 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 r eacted to only PAH. An immunocompetition assay demonstrated that the reacti vity against PAH represents a cross-reactivity with TPH, whereas antibodies against TPH and TH are directed towards epitopes unique for the two enzyme s.