The Department of Bio and Fermentation Convergence Technology, BK21 PLUS Program, Kookmin University, Seoul, Republic of Korea.
Division of Endocrinology and Metabolism, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Sci Rep. 2018 Jun 18;8(1):9262. doi: 10.1038/s41598-018-27600-0.
Graves' disease (GD) is an autoimmune disorder that causes the overproduction of thyroid hormones and consequent cascade of systemic metabolism dysfunction. Moreover, Graves' ophthalmopathy (GO) is the main extrathyroidal manifestation of Graves' disease (GD). The goal of the study was to identify metabolic signatures in association with diagnostic biomarkers of GD without GO and GO, respectively. Ninety metabolites were profiled and analyzed based on a non-targeted primary metabolite profiling from plasma samples of 21 GD patients without GO, 26 subjects with GO, and 32 healthy subjects. Multivariate statistics showed a clear discrimination between healthy controls and disease group (R2Y = 0.518, Q2 = 0.478) and suggested a biomarker panel consisting of 10 metabolites. Among them, most of metabolites showed the positive association with the levels of thyrotropin receptor antibodies. With combination of proline and 1,5-anhydroglucitol, which were identified as GO-specific modulators, the re-constructed biomarker model greatly improved the statistical power and also facilitated simultaneous discrimination among healthy control, GO, and GD without GO groups (AUC = 0.845-0.935). Finally, the comparative analysis of tissue metabolite profiles from GO patients proposed putative metabolic linkage between orbital adipose/connective tissues and the biofluidic consequences, in which fumarate, proline, phenylalanine, and glycerol were coordinately altered with the blood metabolites.
格雷夫斯病（GD）是一种自身免疫性疾病，导致甲状腺激素过度产生，继而导致全身代谢功能紊乱。此外，格雷夫斯眼病（GO）是格雷夫斯病（GD）的主要甲状腺外表现。本研究的目的是分别确定与无 GO 和 GO 的 GD 的诊断生物标志物相关的代谢特征。基于对 21 名无 GO 的 GD 患者、26 名 GO 患者和 32 名健康对照者的血浆样本进行的非靶向初级代谢物特征分析，对 90 种代谢物进行了分析。多变量统计显示健康对照组和疾病组之间有明显的区分（R2Y=0.518，Q2=0.478），并提示由 10 种代谢物组成的生物标志物组合。其中，大多数代谢物与促甲状腺激素受体抗体的水平呈正相关。脯氨酸和 1,5-脱水葡萄糖醇结合后，可作为 GO 特异性调节剂，所构建的生物标志物模型大大提高了统计能力，同时也有助于健康对照组、GO 组和无 GO 的 GD 组之间的同时区分（AUC=0.845-0.935）。最后，对 GO 患者组织代谢谱的比较分析提出了眼眶脂肪/结缔组织与生物流体后果之间的潜在代谢联系，其中延胡索酸、脯氨酸、苯丙氨酸和甘油与血液代谢物协同改变。
