Naskali Emmi, Dettmer Katja, Oefner Peter J, Pereira Pedro A B, Krohn Kai, Auvinen Petri, Ranki Annamari, Kluger Nicolas
Department of Dermatology, Allergology and Venereology, University of Helsinki, and Helsinki University Central Hospital, Helsinki, Finland.
Institute of Functional Genomics, University of Regensburg, Regensburg, Germany.
Endocr Connect. 2019 Jan 1;8(1):69-77. doi: 10.1530/EC-18-0513.
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.
目的 自身免疫性多内分泌腺病-念珠菌病-外胚层营养不良（APECED）患者存在伴有胃肠（GI）功能障碍的肠道自身免疫。患者缺乏肠内分泌（EE）细胞，且具有针对血清素（5-羟色胺，5-HT）生物合成关键酶的循环自身抗体（Aabs）。设计 我们试图测定37名芬兰APECED患者血清中5-HT、色氨酸（Trp）代谢产物和左旋多巴（L-DOPA）的水平，并将其丰度与色氨酸羟化酶（TPH）和芳香酸脱羧酶（AADC）自身抗体的存在、胃肠功能障碍及抑郁症状相关联。我们还对肠道微生物群进行了探索性分析。方法 采用液相色谱-电喷雾电离-串联质谱法（LC-ESI-MS/MS）测定血清5-HT、L-DOPA和Trp代谢产物水平。通过酶联免疫吸附测定法（ELISA）检测TPH和AADC自身抗体。使用结构化的贝克抑郁量表（RBDI）问卷评估抑郁情况。对细菌16S rRNA基因的V3-V4区域进行测序以探索肠道微生物群。结果 与对照组及仅存在AADC自身抗体的患者相比，存在TPH-1（±AADC）自身抗体的APECED患者血清5-HT水平显著降低（130±131 nmol/L vs 686±233 nmol/L，P<0.0001）。5-HT水平降低与便秘相关。埃希氏菌属/志贺氏菌属在肠道微生物群中占比过高。未发现血清Trp、5-HT或L-DOPA水平与RBDI总分、疲劳或睡眠障碍之间存在相关性。结论 这项探索性研究发现血清5-HT水平低与便秘以及TPH-1和AADC自身抗体的存在相关，但与抑郁症状无关。因此，对于出现胃肠症状的APECED患者，应测定血清5-HT、TPH1和AADC自身抗体。
