Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED
Objective: 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 serotoni...
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doaj-76aa1a82178c4a93b9f94949ea98c2602020-11-25T00:12:51ZengBioscientificaEndocrine Connections2049-36142049-36142019-01-01816977https://doi.org/10.1530/EC-18-0513Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECEDEmmi Naskali0Katja Dettmer1Peter J Oefner2Pedro A B Pereira3Kai Krohn4Petri Auvinen5Annamari Ranki6Nicolas Kluger7Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, FinlandInstitute of Functional Genomics, University of Regensburg, Regensburg, GermanyInstitute of Functional Genomics, University of Regensburg, Regensburg, GermanyInstitute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, FinlandClinical Research Institute HUCH Ltd, Biomedicum Helsinki 1, Helsinki, FinlandInstitute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, FinlandDepartment of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, FinlandDepartment of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, FinlandObjective: 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. Design: 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. Methods: 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–V4 regions of the bacterial 16S rRNA gene were sequenced for gut microbiome exploration. Results: Serum 5-HT levels were significantly decreased (130 ± 131 nmol/L vs 686 ± 233 nmol/L, P < 0.0001) in APECED patients with TPH-1 (±AADC) Aabs compared to controls and patients with only AADC Aabs. Reduced 5-HT levels correlated with constipation. The genus Escherichia/Shigella was overrepresented in the intestinal microbiome. No correlation between serum Trp, 5-HT or l-DOPA levels and the RBDI total score, fatigue or sleep disorders was found. Conclusions: 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.https://ec.bioscientifica.com/view/journals/ec/8/1/EC-18-0513.xmlAPECEDserotonindiarrheaconstipationentero-endrocrine cellsPaneth cells |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Emmi Naskali Katja Dettmer Peter J Oefner Pedro A B Pereira Kai Krohn Petri Auvinen Annamari Ranki Nicolas Kluger |
spellingShingle |
Emmi Naskali Katja Dettmer Peter J Oefner Pedro A B Pereira Kai Krohn Petri Auvinen Annamari Ranki Nicolas Kluger Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED Endocrine Connections APECED serotonin diarrhea constipation entero-endrocrine cells Paneth cells |
author_facet |
Emmi Naskali Katja Dettmer Peter J Oefner Pedro A B Pereira Kai Krohn Petri Auvinen Annamari Ranki Nicolas Kluger |
author_sort |
Emmi Naskali |
title |
Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED |
title_short |
Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED |
title_full |
Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED |
title_fullStr |
Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED |
title_full_unstemmed |
Serotonin and tryptophan metabolites, autoantibodies and gut microbiome in APECED |
title_sort |
serotonin and tryptophan metabolites, autoantibodies and gut microbiome in apeced |
publisher |
Bioscientifica |
series |
Endocrine Connections |
issn |
2049-3614 2049-3614 |
publishDate |
2019-01-01 |
description |
Objective: 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.
Design: 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.
Methods: 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–V4 regions of the bacterial 16S rRNA gene were sequenced for gut microbiome exploration.
Results: Serum 5-HT levels were significantly decreased (130 ± 131 nmol/L vs 686 ± 233 nmol/L, P < 0.0001) in APECED patients with TPH-1 (±AADC) Aabs compared to controls and patients with only AADC Aabs. Reduced 5-HT levels correlated with constipation. The genus Escherichia/Shigella was overrepresented in the intestinal microbiome. No correlation between serum Trp, 5-HT or l-DOPA levels and the RBDI total score, fatigue or sleep disorders was found.
Conclusions: 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. |
topic |
APECED serotonin diarrhea constipation entero-endrocrine cells Paneth cells |
url |
https://ec.bioscientifica.com/view/journals/ec/8/1/EC-18-0513.xml |
work_keys_str_mv |
AT emminaskali serotoninandtryptophanmetabolitesautoantibodiesandgutmicrobiomeinapeced AT katjadettmer serotoninandtryptophanmetabolitesautoantibodiesandgutmicrobiomeinapeced AT peterjoefner serotoninandtryptophanmetabolitesautoantibodiesandgutmicrobiomeinapeced AT pedroabpereira serotoninandtryptophanmetabolitesautoantibodiesandgutmicrobiomeinapeced AT kaikrohn serotoninandtryptophanmetabolitesautoantibodiesandgutmicrobiomeinapeced AT petriauvinen serotoninandtryptophanmetabolitesautoantibodiesandgutmicrobiomeinapeced AT annamariranki serotoninandtryptophanmetabolitesautoantibodiesandgutmicrobiomeinapeced AT nicolaskluger serotoninandtryptophanmetabolitesautoantibodiesandgutmicrobiomeinapeced |
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