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Identification of tryptophan hydroxylase as an intestinal autoantigen.

Journal article
Authors Olov Ekwall
H Hedstrand
L Grimelius
J Haavik
J Perheentupa
J Gustafsson
E Husebye
O Kämpe
F Rorsman
Published in Lancet
Volume 352
Issue 9124
Pages 279-83
ISSN 0140-6736
Publication year 1998
Published at
Pages 279-83
Language en
Keywords Adolescent, Adult, Autoantibodies, analysis, Autoantigens, immunology, Autoimmune Diseases, immunology, Blood Donors, Child, DNA, Complementary, Duodenum, immunology, Female, Finland, epidemiology, Genes, Recessive, Humans, Immunohistochemistry, Intestine, Small, immunology, Male, Middle Aged, Norway, epidemiology, Polyendocrinopathies, Autoimmune, classification, epidemiology, genetics, immunology, Sweden, epidemiology, Tryptophan Hydroxylase, immunology
Subject categories Endocrinology, Gastroenterology and Hepatology

Abstract

BACKGROUND: Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder with both endocrine and non-endocrine features. Periodic gastrointestinal dysfunction occurs in 25-30% of APS1 patients. We aimed to identify an intestinal autoantigen. METHODS: A human duodenal cDNA library was immunoscreened with serum samples from APS1 patients. A positive clone was identified and used for in-vitro transcription and translation, followed by immunoprecipitation with serum samples from 80 APS1 patients from Norway, Finland, and Sweden. Sections of normal and APS1-affected small intestine were immunostained with serum from APS1 patients and specific antibodies. An enzyme-inhibition assay was used to characterise the autoantibodies. FINDINGS: We isolated a cDNA clone coding for tryptophan hydroxylase. 48% (38/80) of APS1 patients had antibodies to tryptophan hydroxylase, whereas no reactivity to this antigen was detected in patients with other autoimmune diseases (n=372) or healthy blood donors (n=70). 89% (17/19) of APS1 patients with gastrointestinal dysfunction were positive for antibodies to tryptophan hydroxylase, compared with 34% (21/61) of patients with no gastrointestinal dysfunction (p<0.0001). Serum from antibody-positive APS1 patients specifically immunostained tryptophan-hydroxylase-containing enterochromaffin cells in normal duodenal mucosa. No serotonin-containing cells were seen in duodenal biopsy samples from APS1 patients. Serum from antibody-positive APS1 patients almost completely inhibited activity of tryptophan hydroxylase. INTERPRETATION: Tryptophan hydroxylase is an endogenous intestinal autoantigen in APS1, and there is an association between antibodies to the antigen and gastrointestinal dysfunction. Analysis of antibodies to tryptophan hydroxylase may be a valuable diagnostic tool to predict and monitor gastrointestinal dysfunction in APS1.

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