类风湿性关节炎滑液中色氨酸相关代谢组学特征的下调

Downregulation of Tryptophan-related Metabolomic Profile in Rheumatoid Arthritis Synovial Fluid.

作者信息

Kang Kwi Young, Lee Soo Hyun, Jung Seung Min, Park Sung-Hwan, Jung Byung-Hwa, Ju Ji Hyeon

机构信息

From the Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul; Division of Rheumatology, Department of Internal Medicine, College of Medicine, Incheon Saint Mary's Hospital, The Catholic University of Korea, Incheon; Department of Medical Records and Health Information Management, College of Nursing and Health, Kongju National University, Chungnam; Molecular Recognition Research Center, Korea Institute of Science and Technology, Seoul; Division of Biological Chemistry, University of Science and Technology, Daejeon, South Korea.K.Y. Kang, PhD, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Division of Rheumatology, Department of Internal Medicine, College of Medicine, Incheon Saint Mary's Hospital, The Catholic University of Korea; S.H. Lee, PhD, Department of Medical Records and Health Information Management, College of Nursing and Health, Kongju National University; S.M. Jung, MD; S.H. Park, PhD, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea; B.H. Jung, PhD, Molecular Recognition Research Center, Korea Institute of Science and Technology, Division of Biological Chemistry, University of Science and Technology; J.H. Ju, PhD, Division of Rheumatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea.

出版信息

J Rheumatol. 2015 Nov;42(11):2003-11. doi: 10.3899/jrheum.141505. Epub 2015 Sep 1.

DOI:10.3899/jrheum.141505

PMID:26329338

Abstract

OBJECTIVE

Synovial fluid (SF) is one of the most important materials that reflect the pathophysiological process of arthritis. A metabolomic and lipidomic study of SF was performed with the aim of identifying tentative diagnostic markers or therapeutic candidates for rheumatoid arthritis (RA).

METHODS

SF was aspirated from 10 patients with RA and 10 patients with osteoarthritis (OA). RA SF and OA SF were collected and analyzed by ultraperformance liquid chromatography quadruple time-of-flight mass spectrometry. Associations among clinical variables, laboratory results, and metabolic profiles were investigated.

RESULTS

The metabolic pathways for carnitine, tryptophan, phenylalanine, arachidonic acid, and glycophospholipid were significantly upregulated in OA SF. The metabolic pathways for taurine, cholesterol ester, and the β-oxidation of pristine acid, linolenic acid, and sphingolipid were activated more in RA SF than in OA SF. In particular, the tryptophan pathway, which comprises kynurenine, indoleacetic acid, indole acetaldehyde, and N'-formylkynurenine, was downregulated. Interestingly, the levels of tryptophan metabolites kynurenine and N'-formylkynurenine, which are involved in immune tolerance, were significantly lower in RA SF compared with OA SF (p < 0.05), but the opposite pattern was observed for erythrocyte sedimentation rate (p < 0.01) and the levels of C-reactive protein (CRP; p < 0.01), rheumatoid factor (p < 0.01), and anticyclic citrullinated peptide antibody (p < 0.05). Kynurenine concentration correlated inversely with CRP concentration in RA SF but not in OA SF (r -0.65, p < 0.05).

CONCLUSION

Advances in metabolomic techniques enabled us to delineate distinctive metabolic and lipidomic profiles in RA SF and OA SF. RA SF and OA SF showed distinct metabolic profiles.

摘要

目的

滑液（SF）是反映关节炎病理生理过程的最重要物质之一。对滑液进行代谢组学和脂质组学研究，旨在确定类风湿性关节炎（RA）的初步诊断标志物或治疗候选物。

方法

从10例类风湿性关节炎患者和10例骨关节炎（OA）患者中抽取滑液。收集类风湿性关节炎滑液和骨关节炎滑液，并用超高效液相色谱四极杆飞行时间质谱进行分析。研究临床变量、实验室结果和代谢谱之间的关联。

结果

肉碱、色氨酸、苯丙氨酸、花生四烯酸和糖磷脂的代谢途径在骨关节炎滑液中显著上调。牛磺酸、胆固醇酯以及原酸、亚麻酸和鞘脂的β-氧化代谢途径在类风湿性关节炎滑液中比在骨关节炎滑液中更活跃。特别是，由犬尿氨酸、吲哚乙酸、吲哚乙醛和N'-甲酰犬尿氨酸组成的色氨酸途径被下调。有趣的是，与免疫耐受有关的色氨酸代谢产物犬尿氨酸和N'-甲酰犬尿氨酸在类风湿性关节炎滑液中的水平显著低于骨关节炎滑液（p<0.05），但红细胞沉降率（p<0.01）以及C反应蛋白（CRP；p<0.01）、类风湿因子（p<0.01）和抗环瓜氨酸肽抗体（p<0.05）的水平则呈现相反的模式。在类风湿性关节炎滑液中，犬尿氨酸浓度与CRP浓度呈负相关，而在骨关节炎滑液中则无此相关性（r -0.65，p<0.05）。