IDENTIFICATION OF TRYPTOPHAN-HYDROXYLASE AS AN INTESTINAL AUTOANTIGEN

Background Autoimmune polyendocrine syndrome type 1 (APS1) is an autos omal recessive disorder with both endocrine and non-endocrine features . Periodic gastrointestinal dysfunction occurs in 25-30% of APS1 patie nts. We aimed to identify an intestinal autoantigen. Methods A human d uodenal cDNA library was immunoscreened with serum samples from APS1 p atients. A positive clone was identified and used for in-vitro transcr iption and translation, followed by immunoprecipitation with serum sam ples from 80 APS1 patients from Norway, Finland, and Sweden. Sections of normal and APS1-affected small intestine were immunostained with se rum from APS1 patients and specific antibodies. An enzyme-inhibition a ssay was used to characterise the autoantibodies. Findings We isolated a cDNA clone coding for tryptophan hydroxylase. 48% (38/80) of APS1 p atients had antibodies to tryptophan hydroxylase, whereas no reactivit y to this antigen was detected in patients with other autoimmune disea ses (n=372) or healthy blood donors (n=70). 89% (17/19) of APS1 patien ts with gastrointestinal dysfunction were positive for antibodies to t ryptophan hydroxylase, compared with 34% (21/61) of patients with no g astrointestinal dysfunction (p<0.0001). Serum from antibody-positive A PSI patients specifically immunostained tryptophan-hydroxylase-contain ing enterochromaffin cells in normal duodenal mucosa. No serotonin-con taining cells were seen in duodenal biopsy samples from APS1 patients. Serum from antibody-positive APS1 patients almost completely inhibite d activity of tryptophan hydroxylase, Interpretation Tryptophan hydrox ylase is an endogenous intestinal autoantigen in APS1, and there is an association between antibodies to the antigen and gastrointestinal dy sfunction. Analysis of antibodies to tryptophan hydroxylase may be a v aluable diagnostic tool to predict and monitor gastrointestinal dysfun ction in APS1.