Metabolic discrimination of synovial fluid between rheumatoid arthritis and osteoarthritis using gas chromatography/time-of-flight mass spectrometry

Sooah Kim1, Jiwon Hwang2, Jungyeon Kim3, Sun-Hee Lee3, Yu Eun Cheong3, Seulkee Lee4, Kyoung Heon Kim3,5, Hoon-Suk Cha4
1Department of Environment Science & Biotechnology, Jeonju University, Jeonju, Republic of Korea
2Division of Rheumatology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea
3Department of Biotechnology, Graduate School, Korea University, Seoul, Republic of Korea
4Division of Rheumatology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
5Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea

Tóm tắt

Rheumatoid arthritis (RA) and osteoarthritis (OA) are clinicopathologically different. We aimed to assess the feasibility of metabolomics in differentiating the metabolite profiles of synovial fluid between RA and OA using gas chromatography/time-of-flight mass spectrometry. We first compared the global metabolomic changes in the synovial fluid of 19 patients with RA and OA. Partial least squares-discriminant, hierarchical clustering, and univariate analyses were performed to distinguish metabolites of RA and OA. These findings were then validated using synovial fluid samples from another set of 15 patients with RA and OA. We identified 121 metabolites in the synovial fluid of the first 19 samples. The score plot of PLS-DA showed a clear separation between RA and OA. Twenty-eight crucial metabolites, including hypoxanthine, xanthine, adenosine, citrulline, histidine, and tryptophan, were identified to be capable of distinguishing RA metabolism from that of OA; these were found to be associated with purine and amino acid metabolism. Our results demonstrated that metabolite profiling of synovial fluid could clearly discriminate between RA and OA, suggesting that metabolomics may be a feasible tool to assist in the diagnosis and advance the comprehension of pathological processes for diseases.

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Tài liệu tham khảo

Adlesic, M., Verdrengh, M., Bokarewa, M., Dahlberg, L., Foster, S. J., & Tarkowski, A. (2007). Histamine in rheumatoid arthritis. Scandinavian Journal of Immunology, 65, 530–537. https://doi.org/10.1111/j.1365-3083.2007.01938.x

Ahn, J. K., Kim, S., Hwang, J., Kim, J., Kim, K. H., & Cha, H. S. (2016). GC/TOF-MS-based metabolomic profiling in cultured fibroblast-like synoviocytes from rheumatoid arthritis. Joint, Bone, Spine, 83, 707–713.

Ahn, J. K., Kim, S., Kim, J., Hwang, J., Kim, K. H., & Cha, H. S. (2015). A comparative metabolomic evaluation of Behcet’s disease with arthritis and seronegative arthritis using synovial fluid. PLoS ONE. https://doi.org/10.1371/journal.pone.0135856

Altman, R., et al. (1986). Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the knee. Arthritis and Rheumatism, 29, 1039–1049. https://doi.org/10.1002/art.1780290816

Anderson, J. R., et al. (2018). H1 NMR metabolomics identifies underlying inflammatory pathology in osteoarthritis and rheumatoid arthritis synovial joints. Journal of Proteome Research, 17, 3780–3790. https://doi.org/10.1021/acs.jproteome.8b00455

Appelboom, T., Mandelbaum, I., & Vertongen, F. (1985). Purine enzyme levels in rheumatoid arthritis. Journal of Rheumatology, 12, 1075–1078.

Arnett, F. C., et al. (1988). The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis and Rheumatism, 31, 315–324. https://doi.org/10.1002/art.1780310302

Attur, M., Krasnokutsky-Samuels, S., Samuels, J., & Abramson, S. B. (2013). Prognostic biomarkers in osteoarthritis. Current Opinion in Rheumatology, 25, 136–144. https://doi.org/10.1097/BOR.0b013e32835a9381

Babcock, T. A., & Carlin, J. M. (2000). Transcriptional activation of indoleamine dioxygenase by interleukin 1 and tumor necrosis factor alpha in interferon-treated epithelial cells. Cytokine, 12, 588–594. https://doi.org/10.1006/cyto.1999.0661

Balakrishnan, L., et al. (2014). Differential proteomic analysis of synovial fluid from rheumatoid arthritis and osteoarthritis patients. Clinical Proteomics. https://doi.org/10.1186/1559-0275-11-1

Borenstein, D. G., Gibbs, C. A., & Jacobs, R. P. (1982). Gas-liquid chromatographic analysis of synovial fluid. Arthritis and Rheumatism, 25, 947–953. https://doi.org/10.1002/art.1780250806

Chang, X., et al. (2005). Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial tissue of rheumatoid arthritis. Rheumatology, 44, 40–50. https://doi.org/10.1093/rheumatology/keh414

Edwards, N. L., Magilavy, D. B., Cassidy, J. T., & Fox, I. H. (1978). Lymphocyte ecto-5′-nucleotidase deficiency in agammaglobulinemia. Science, 201, 628–630. https://doi.org/10.1126/science.27864

Gerber, D. A. (1975). Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity. Journal of Clinical Investigation, 55, 1164–1173. https://doi.org/10.1172/jci108033

Gibofsky, A. (2012). Overview of epidemiology, pathophysiology, and diagnosis of rheumatoid arthritis. The American Journal of Managed Care, 18, S295-302.

Goldring, M. B. (2012). Articular cartilage degradation in osteoarthritis. HSS Journal, 8, 7–9.

Hua, S. S., & Dias, T. H. (2016). Hypoxia-inducible factor (HIF) as a target for novel therapies in rheumatoid arthritis. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2016.00184

Hugle, T., et al. (2012). Synovial fluid metabolomics in different forms of arthritis assessed by nuclear magnetic resonance spectroscopy. Clinical and Experimental Rheumatology, 30, 240–245.

Hui, A. Y., McCarty, W. J., Masuda, K., Firestein, G. S., & Sah, R. L. (2012). A systems biology approach to synovial joint lubrication in health, injury, and disease. Wiley Interdisciplinary Reviews-Systems Biology and Medicine, 4, 15–37. https://doi.org/10.1002/wsbm.157

Jafarzadeh, S. R., & Felson, D. T. (2018). Updated estimates suggest a much higher prevalence of arthritis in United States adults than previous ones. Arthritis & Rheumatology, 70, 185–192. https://doi.org/10.1002/art.40355

Kellgren, J. H., & Lawrence, J. S. (1957). Radiological assessment of osteo-arthrosis. Annals of the Rheumatic Diseases, 16, 494–502. https://doi.org/10.1136/ard.16.4.494

Kim, K. W., Kim, B. M., Lee, K. A., Lee, S. H., Firestein, G. S., & Kim, H. R. (2017). Histamine and histamine H4 receptor promotes osteoclastogenesis in rheumatoid arthritis. Scientific Reports. https://doi.org/10.1038/s41598-017-01101-y

Kim, S., Hwang, J., Kim, J., Ahn, J. K., Cha, H. S., & Kim, K. H. (2017). Metabolite profiles of synovial fluid change with the radiographic severity of knee osteoarthritis. Joint, Bone, Spine, 84, 605–610. https://doi.org/10.1016/j.jbspin.2016.05.018

Kim, S., Hwang, J., Xuan, J., Jung, Y. H., Cha, H. S., & Kim, K. H. (2014). Global metabolite profiling of synovial fluid for the specific diagnosis of rheumatoid arthritis from other inflammatory arthritis. PLoS ONE. https://doi.org/10.1371/journal.pone.0097501

Kind, T., et al. (2009). FiehnLib: Mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography/mass spectrometry. Analytical Chemistry, 81, 10038–10048. https://doi.org/10.1021/ac9019522

Kinloch, A., et al. (2008). Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis. Arthritis and Rheumatism, 58, 2287–2295. https://doi.org/10.1002/art.23618

Kwidzinski, E., & Bechmann, I. (2007). IDO expression in the brain: A double-edged sword. Journal of Molecular Medicine-Jmm, 85, 1351–1359. https://doi.org/10.1007/s00109-007-0229-7

Li, Z. C., et al. (2014). Functional annotation of rheumatoid arthritis and osteoarthritis associated genes by integrative genome-wide gene expression profiling analysis. PLoS ONE. https://doi.org/10.1371/journal.pone.0085784

Marinello, E., Carlucci, F., Tabucchi, A., Leoncini, R., Pizzichini, M., & Pagani, R. (1994). The purine nucleotide content of lymphocytes from patients with rheumatoid arthritis. International Journal of Clinical Pharmacology Research, 14, 57–63.

McInnes, I., & Schett, G. (2011). The pathogenesis of rheumatoid arthritis. New England Journal of Medicine, 365, 2205–2219.

Murata, K., et al. (2010). Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Research & Therapy. https://doi.org/10.1186/ar3013

Poss, W. B., Huecksteadt, T. P., Panus, P. C., Freeman, B. A., & Hoidal, J. R. (1996). Regulation of xanthine dehydrogenase and xanthine oxidase activity by hypoxia. American Journal of Physiology-Lung Cellular and Molecular Physiology, 270, L941–L946.

Saeed, A. I., et al. (2006). TM4 microarray software suite. Methods in Enzymology, 411, 134–193. https://doi.org/10.1016/s0076-6879(06)11009-5

Schroecksnadel, K., et al. (2003). Increased degradation of tryptophan in blood of patients with rheumatoid arthritis. Journal of Rheumatology, 30, 1935–1939.

Schroecksnadel, K., Winkler, C., Duftner, C., Wirleitner, B., Schirmer, M., & Fuchs, D. (2006). Tryptophan degradation increases with stage in patients with rheumatoid arthritis. Clinical Rheumatology, 25, 334–337. https://doi.org/10.1007/s10067-005-0056-6

Simoni, R. E., Gomes, L., Scalco, F. B., Oliveira, C. P. H., Neto, F. R. A., & de Oliveira, M. L. C. (2007). Uric acid changes in urine and plasma: An effective tool in screening for purine inborn errors of metabolism and other pathological conditions. Journal of Inherited Metabolic Disease, 30, 295–309. https://doi.org/10.1007/s10545-007-0455-8

Skogerson, K., Wohlgemuth, G., Barupal, D. K., & Fiehn, O. (2011). The volatile compound BinBase mass spectral database. BMC Bioinformatics. https://doi.org/10.1186/1471-2105-12-321

Tanaka, S., Sohen, S., & Fukuda, K. (1997). A role for histamine receptors in rheumatoid arthritis. Seminars in Arthritis and Rheumatism, 26, 824–833. https://doi.org/10.1016/s0049-0172(97)80026-1

Tetlow, L. C., & Woolley, D. E. (2005). Histamine, histamine receptors (H-1 and H-2), and histidine decarboxylase expression by chondrocytes of osteoarthritic cartilage: An immunohistochemical study. Rheumatology International, 26, 173–178. https://doi.org/10.1007/s00296-005-0622-x

Umetrics, A. B. (2005). User's Guide to SIMCA-P, SIMCA-P+ version 11.0. Umeå (Sweden), Umetrics AB.

van den Berg, R. A., Hoefsloot, H. C. J., Westerhuis, J. A., Smilde, A. K., & van der Werf, M. J. (2006). Centering, scaling, and transformations: Improving the biological information content of metabolomics data. BMC Genomics. https://doi.org/10.1186/1471-2164-7-142

van Ede, A. E., Laan, R., De Abreu, R. A., Stegeman, A. B. J., & van de Putte, L. B. A. (2002). Purine enzymes in patients with rheumatoid arthritis treated with methotrexate. Annals of the Rheumatic Diseases, 61, 1060–1064. https://doi.org/10.1136/ard.61.12.1060

van Venrooij, W. J., & Pruijn, G. J. (2000). Citrullination: A small change for a protein with great consequences for rheumatoid arthritis. Arthritis Research & Therapy, 2, 249–251.

Williams, R. O. (2013). Exploitation of the IDO pathway in the therapy of rheumatoid arthritis. International Journal of Tryptophan Research. https://doi.org/10.4137/ijtr.s11737

Xia, J. G., & Wishart, D. S. (2010). MSEA: A web-based tool to identify biologically meaningful patterns in quantitative metabolomic data. Nucleic Acids Research, 38, W71–W77. https://doi.org/10.1093/nar/gkq329

Zheng, K. D., et al. (2017). Global and Targeted Metabolomics of Synovial Fluid Discovers Special Osteoarthritis Metabolites. Journal of Orthopaedic Research, 35, 1973–1981. https://doi.org/10.1002/jor.23482