{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:40:02Z","timestamp":1785404402438,"version":"3.56.0"},"reference-count":26,"publisher":"Bioscientifica","issue":"1","license":[{"start":{"date-parts":[[2019,1,1]],"date-time":"2019-01-01T00:00:00Z","timestamp":1546300800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,1]]},"abstract":"\n Objective<\/jats:title>\n Intestinal autoimmunity with gastrointestinal (GI) dysfunction has been shown in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Patients lack entero-endocrine (EE) cells and have circulating autoantibodies (Aabs) against critical enzymes in serotonin (5-HT) biosynthesis.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n We sought to determine the serum levels of 5-HT, tryptophan (Trp) metabolites and L-DOPA in 37 Finnish APECED patients and to correlate their abundance with the presence of TPH and AADC Aabs, GI dysfunction and depressive symptoms. We also performed an exploratory analysis of the gut microbiome.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Serum 5-HT, L-DOPA and Trp metabolite levels were determined by liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS\/MS). TPH and AADC Aabs were measured by ELISA. Depression was assessed with a structured RBDI questionnaire. The V3\u2013V4 regions of the bacterial 16S rRNA gene were sequenced for gut microbiome exploration.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Serum 5-HT levels were significantly decreased (130\u2009\u00b1\u2009131\u2009nmol\/L vs 686\u2009\u00b1\u2009233\u2009nmol\/L,\n P<\/jats:italic>\n \u2009<\u20090.0001) in APECED patients with TPH-1 (\u00b1AADC) Aabs compared to controls and patients with only AADC Aabs. Reduced 5-HT levels correlated with constipation. The genus\n Escherichia\/Shigella<\/jats:italic>\n was overrepresented in the intestinal microbiome. No correlation between serum Trp, 5-HT or\n l<\/jats:sc>\n -DOPA levels and the RBDI total score, fatigue or sleep disorders was found.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This exploratory study found low serum levels of 5-HT to be associated with constipation and the presence of TPH-1 and AADC Aabs, but not with symptoms of depression. Hence, serum 5-HT, TPH1 and AADC Aabs should be determined in APECED patients presenting with GI symptoms.<\/jats:p>\n <\/jats:sec>","DOI":"10.1530\/ec-18-0513","type":"journal-article","created":{"date-parts":[[2019,1,4]],"date-time":"2019-01-04T10:42:50Z","timestamp":1546598570000},"page":"69-77","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":5,"title":["Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED"],"prefix":"10.1530","volume":"8","author":[{"given":"Emmi","family":"Naskali","sequence":"first","affiliation":[{"name":"1Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Dettmer","sequence":"additional","affiliation":[{"name":"2Institute of Functional Genomics, University of Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J","family":"Oefner","sequence":"additional","affiliation":[{"name":"2Institute of Functional Genomics, University of Regensburg, Regensburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro A B","family":"Pereira","sequence":"additional","affiliation":[{"name":"3Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Krohn","sequence":"additional","affiliation":[{"name":"4Clinical Research Institute HUCH Ltd, Biomedicum Helsinki 1, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petri","family":"Auvinen","sequence":"additional","affiliation":[{"name":"3Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamari","family":"Ranki","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Kluger","sequence":"additional","affiliation":[{"name":"1Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref151","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1007\/s00216-011-5436-y","article-title":"Quantitative profiling of tryptophan metabolites in serum, urine, and cell culture supernatants by liquid chromatography-tandem mass spectrometry","volume":"401","year":"2011","journal-title":"Analytical and Bioanalytical Chemistry"},{"key":"ref211","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","year":"2014","journal-title":"Genome Biology"},{"key":"ref201","doi-asserted-by":"crossref","first-page":"e61217","DOI":"10.1371\/journal.pone.0061217","article-title":"phyloseq: an R package for reproducible interactive analysis and graphics of microbiome census data","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"3546","DOI":"10.1210\/jc.2017-00139","article-title":"Expanding the phenotypic and genotypic landscape of autoimmune polyendocrine syndrome type 1","volume":"102","year":"2017","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref161","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.parkreldis.2017.02.026","article-title":"Oral and nasal microbiota in Parkinson\u2019s disease","volume":"38","year":"2017","journal-title":"Parkinsonism and Related Disorders"},{"key":"ref181","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","year":"2011","journal-title":"EMBnet.journal"},{"key":"ref231","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1038\/ni.3780","article-title":"Regulation of inflammation by microbiota interactions with the host","volume":"18","year":"2017","journal-title":"Nature Immunology"},{"key":"ref261","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.clim.2014.10.010","article-title":"Disease specificity of anti-tryptophan hydroxylase-1 and anti-AIE-75 autoantibodies in APECED and IPEX syndrome","volume":"156","year":"2015","journal-title":"Clinical Immunology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"976","DOI":"10.3389\/fimmu.2017.00976","article-title":"Autoantibody repertoire in APECED patients targets two distinct subgroups of proteins","volume":"8","year":"2017","journal-title":"Frontiers in Immunology"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.clim.2015.03.012","article-title":"Gastrointestinal immunity against tryptophan hydroxylase-1, aromatic L-amino-acid decarboxylase, AIE-75,villin and Paneth cells in APECED","volume":"158","year":"2015","journal-title":"Clinical Immunology"},{"key":"ref251","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1053\/j.gastro.2015.05.009","article-title":"Gastrointestinal autoimmunity associated with loss of central tolerance to enteric \u03b1-defensins","volume":"149","year":"2015","journal-title":"Gastroenterology"},{"key":"ref191","doi-asserted-by":"crossref","first-page":"7537","DOI":"10.1128\/AEM.01541-09","article-title":"Introducing mothur: open-source, platform-independent,community-supported software for describing and comparing microbial communities","volume":"75","year":"2009","journal-title":"Applied and Environmental Microbiology"},{"key":"ref221","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1097\/MCG.0b013e31827356e1","article-title":"Gastrointestinal manifestations in APECED syndrome","volume":"47","year":"2013","journal-title":"Journal of Clinical Gastroenterology"},{"key":"ref61","first-page":"147","article-title":"Autoantibodies against aromatic L-amino acid decarboxylase in autoimmune polyendocrine syndrome type I","volume":"82","year":"1997","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s10875-015-0176-y","article-title":"Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy","volume":"35","year":"2015","journal-title":"Journal of Clinical Immunology"},{"key":"ref71","first-page":"313","article-title":"Autoantibodies to human tryptophan hydroxylase and aromatic L-amino acid decarboxylase","volume":"150","year":"2004","journal-title":"European Journal of Endocrinology"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1210\/jc.2012-2734","article-title":"Tryptophan hydroxylase autoantibodies as markers of a distinct autoimmune gastrointestinal component of autoimmune polyendocrine syndrome type 1","volume":"98","year":"2013","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1530\/EC-17-0022","article-title":"Autoimmune polyendocrine syndrome type 1 in an Indian cohort: a longitudinal study","volume":"6","year":"2017","journal-title":"Endocrine Connections"},{"key":"ref131","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/imm.12933","article-title":"Impacts of microbiome metabolites on immune regulation and autoimmunity","volume":"154","year":"2018","journal-title":"Immunology"},{"key":"ref01","doi-asserted-by":"crossref","first-page":"2843","DOI":"10.1210\/jc.2005-2611","article-title":"Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"91","year":"2006","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref11","first-page":"e88782","article-title":"Redefined clinical features and diagnostic criteria in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy","volume":"1","year":"2016","journal-title":"JCI Insight"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1111\/cen.12087","article-title":"What is the burden of living with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) in 2012? A health-related quality-of-life assessment in Finnish patients","volume":"79","year":"2013","journal-title":"Clinical Endocrinology"},{"key":"ref101","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1038\/nrgastro.2017.51","article-title":"Non-conventional features of peripheral serotonin signalling \u2013 the gut and beyond","volume":"14","year":"2017","journal-title":"Nature Reviews Gastroenterology and Hepatology"},{"key":"ref141","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbi.2017.01.016","article-title":"Microbes and mental health: a review","volume":"66","year":"2017","journal-title":"Brain, Behavior, and Immunity"},{"key":"ref241","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/nature24661","article-title":"A gut bacterial pathway metabolizes aromatic amino acids into nine circulating metabolites","volume":"551","year":"2017","journal-title":"Nature"},{"key":"ref91","doi-asserted-by":"publisher","first-page":"201297","DOI":"10.1210\/jc.2011-2044","article-title":"PosovszkyCLahrGvon Loss of EE cells in autoimmune - polyendocrine - candidiasis ectodermal dystrophy syndrome with gastrointestinal dysfunction of and https org","author":"APECED","journal-title":"Journal Clinical Endocrinology Metabolism"}],"container-title":["Endocrine Connections"],"original-title":[],"link":[{"URL":"https:\/\/ec.bioscientifica.com\/view\/journals\/ec\/8\/1\/EC-18-0513.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ec.bioscientifica.com\/downloadpdf\/journals\/ec\/8\/1\/EC-18-0513.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:43:15Z","timestamp":1784554995000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/ec\/article\/8\/1\/69-77\/418"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,1]]},"references-count":26,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1530\/ec-18-0513","relation":{},"ISSN":["2049-3614"],"issn-type":[{"value":"2049-3614","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,1]]}}}