Shimizu Hiroyuki, Usui Yoshihiko, Asakage Masaki, Nezu Naoya, Wakita Ryo, Tsubota Kinya, Sugimoto Masahiro, Goto Hiroshi
Department of Ophthalmology, Tokyo Medical University, Tokyo 160-0023, Japan.
Health Promotion and Preemptive Medicine, Research and Development Center for Minimally Invasive Therapies, Institute of Medical Sciences, Tokyo Medical University, Tokyo 160-8402, Japan.
J Clin Med. 2020 Dec 6;9(12):3955. doi: 10.3390/jcm9123955.
The activities of various metabolic pathways can influence the pathogeneses of autoimmune diseases, and intrinsic metabolites can potentially be used to diagnose diseases. However, the metabolomic analysis of patients with uveitis has not yet been conducted. Here, we profiled the serum metabolomes of patients with three major forms of uveitis (Behҫet's disease (BD), sarcoidosis, and Vogt-Koyanagi-Harada disease (VKH)) to identify potential biomarkers. This study included 19 BD, 20 sarcoidosis, and 15 VKH patients alongside 16 healthy control subjects. The metabolite concentrations in their sera were quantified using liquid chromatography with time-of-flight mass spectrometry. The discriminative abilities of quantified metabolites were evaluated by four comparisons: control vs. three diseases, and each disease vs. the other two diseases (such as sarcoidosis vs. BD + VKH). Among 78 quantified metabolites, 24 kinds of metabolites showed significant differences in these comparisons. Four multiple logistic regression models were developed and validated. The area under the receiver operating characteristic (ROC) curve (AUC) in the model to discriminate disease groups from control was 0.72. The AUC of the other models to discriminate sarcoidosis, BD, and VKH from the other two diseases were 0.84, 0.83, and 0.73, respectively. This study provides potential diagnostic abilities of sarcoidosis, BD, and VKH using routinely available serum samples that can be collected with minimal invasiveness.
各种代谢途径的活动可影响自身免疫性疾病的发病机制,内源性代谢物有可能用于疾病诊断。然而,尚未对葡萄膜炎患者进行代谢组学分析。在此,我们对三种主要类型葡萄膜炎(白塞病(BD)、结节病和小柳原田病(VKH))患者的血清代谢组进行了分析,以确定潜在的生物标志物。本研究纳入了19例BD患者、20例结节病患者和15例VKH患者,以及16名健康对照者。使用液相色谱-飞行时间质谱法定量测定他们血清中的代谢物浓度。通过四项比较评估定量代谢物的判别能力:对照组与三种疾病组比较,以及每种疾病与其他两种疾病比较(如结节病与BD+VKH比较)。在78种定量代谢物中,有24种代谢物在这些比较中显示出显著差异。建立并验证了四个多元逻辑回归模型。区分疾病组与对照组的模型中,受试者工作特征(ROC)曲线下面积(AUC)为0.72。区分结节病、BD和VKH与其他两种疾病的其他模型的AUC分别为0.84、0.83和0.73。本研究提供了利用常规可得的血清样本对结节病、BD和VKH进行潜在诊断的能力,这些样本可以通过微创方式采集。