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


CONCLUSIONS
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.
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.
Kwi Young
KY
Kang
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.
Soo Hyun
SH
Lee
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.
Seung Min
SM
Jung
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.
Sung-Hwan
SH
Park
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. juji@catholic.ac.kr jbhluck@kist.re.kr.
Byung-Hwa
BH
Jung
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. juji@catholic.ac.kr jbhluck@kist.re.kr.
Ji Hyeon
JH
Ju
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000503:physiopathology; D001323:Autoantibodies / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D010003:Osteoarthritis / Q000097:blood* / Q000503:physiopathology; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013582:Synovial Fluid / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism*
D001323:Autoantibodies; D015415:Biomarkers; D014364:Tryptophan; D002097:C-Reactive Protein
MASS SPECTROMETRY; METABOLOMICS; OSTEOARTHRITIS; RHEUMATOID ARTHRITIS; SYNOVIAL FLUID; TRYPTOPHAN