{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:19:04Z","timestamp":1777569544172,"version":"3.51.4"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T00:00:00Z","timestamp":1598832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K21834"],"award-info":[{"award-number":["20K21834"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H01021"],"award-info":[{"award-number":["19H01021"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP20km0405211"],"award-info":[{"award-number":["JP20km0405211"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP20ek0109413"],"award-info":[{"award-number":["JP20ek0109413"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP20ek0410075"],"award-info":[{"award-number":["JP20ek0410075"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP20gm4010006"],"award-info":[{"award-number":["JP20gm4010006"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"AMED","doi-asserted-by":"publisher","award":["JP20km0405217"],"award-info":[{"award-number":["JP20km0405217"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Bioinformatics Initiative of Osaka University Graduate School of Medicine"},{"name":"Immunology Frontier Research Center"},{"DOI":"10.13039\/501100004206","name":"Osaka University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004206","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Novel biomarkers of rheumatoid arthritis (RA), in addition to antibodies against cyclic citrullinated peptides, are required. Metabolome analysis is a promising approach to identify metabolite biomarkers for clinical diagnosis. We adopted a comprehensive non-targeted metabolomics approach combining capillary electrophoresis time-of-flight mass spectrometry (TOFMS) and liquid chromatography TOFMS. We constructed metabolomics profiling of 286 plasma samples of a Japanese population [92 RA patients, 13 systemic lupus erythematosus (SLE) patients and 181 healthy controls). RA case\u2013control association tests showed that seven metabolites exhibited significantly increased levels in RA samples compared with controls (P &amp;lt; 1.0 \u00d7 10\u22124; UTP, ethanolamine phosphate, ATP, GDP, ADP, 6-aminohexanoic acid and taurine), whereas one exhibited a decreased level (xanthine). The plasma levels of these eight metabolites were not significantly different between seropositive and seronegative RA patients (P &amp;gt; 0.05; n = 68 and 24, respectively). The four nucleotide levels (UTP, ATP, GDP and ADP) were significantly higher in the non-treatment patients in comparison between patients with and without treatment (P &amp;lt; 0.014; n = 57 and 35, respectively). Furthermore, we found that none of the four nucleotide levels showed significant differences in SLE case\u2013control association tests (P &amp;gt; 0.2; 13 patients with SLE and the 181 shared controls) and psoriatic arthritis (PsA) case\u2013control association tests (P &amp;gt; 0.11; 42 patients with PsA and 38 healthy controls), indicating disease specificity in RA. In conclusion, our large-scale metabolome analysis demonstrated the increased plasma nucleotide levels in RA patients, which could be used as potential clinical biomarkers of RA, especially for seronegative RA.<\/jats:p>","DOI":"10.1093\/intimm\/dxaa059","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T19:14:15Z","timestamp":1598469255000},"page":"119-124","source":"Crossref","is-referenced-by-count":18,"title":["Increased levels of plasma nucleotides in patients with rheumatoid arthritis"],"prefix":"10.1093","volume":"33","author":[{"given":"Toshihiro","family":"Kishikawa","sequence":"first","affiliation":[{"name":"Department of Statistical Genetics, Osaka University Graduate School of Medicine , Suita, Japan"},{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichi","family":"Maeda","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine , Suita, Japan"},{"name":"Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuro","family":"Nii","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine , Suita, Japan"},{"name":"Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3966-3437","authenticated-orcid":false,"given":"Noriko","family":"Arase","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Statistical Genetics, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Statistical Genetics, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenichi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Statistical Genetics, Osaka University Graduate School of Medicine , Suita, Japan"},{"name":"Department of Pediatrics, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuo","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Statistical Genetics, Osaka University Graduate School of Medicine , Suita, Japan"},{"name":"Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kotaro","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Statistical Genetics, Osaka University Graduate School of Medicine , Suita, Japan"},{"name":"Department of Neurology, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeyoshi","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Orthopedics\/Rheumatology, NHO Osaka Minami Medical Center , Kawachinagano, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masato","family":"Matsushita","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Allergology, Saiseikai Senri Hospital , Suita, Japan"},{"name":"Rheumatology and Allergology, NHO Osaka Minami Medical Center , Kawachinagano, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidetoshi","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Rheumatology and Allergology, NHO Osaka Minami Medical Center , Kawachinagano, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiko","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Rheumatology and Allergology, NHO Osaka Minami Medical Center , Kawachinagano, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Tsunoda","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Sumitomo Hospital , Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiro","family":"Ohshima","sequence":"additional","affiliation":[{"name":"Rheumatology and Allergology, NHO Osaka Minami Medical Center , Kawachinagano, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Narazaki","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Ogata","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Internal Medicine, Daini Osaka Police Hospital , Osaka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiko","family":"Saeki","sequence":"additional","affiliation":[{"name":"Rheumatology and Allergology, NHO Osaka Minami Medical Center , Kawachinagano, Japan"},{"name":"Clinical Research, NHO Osaka Minami Medical Center , Kawachinagano, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hidenori","family":"Inohara","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, Osaka University Graduate School of Medicine , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Kumanogoh","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine and Clinical Immunology, Osaka University Graduate School of Medicine , Suita, Japan"},{"name":"Department of Immunopathology, Immunology Frontier Research Center, Osaka University , Suita, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyoshi","family":"Takeda","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University Graduate School of Medicine , Suita, Japan"},{"name":"WPI Immunology Frontier 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Rheumatol."},{"key":"2023120103434977500_CIT0005","doi-asserted-by":"crossref","first-page":"7328","DOI":"10.1038\/s41598-017-06767-y","article-title":"Decreased long-chain acylcarnitines from insufficient beta-oxidation as potential early diagnostic markers for Parkinson\u2019s disease","volume":"7","author":"Saiki","year":"2017","journal-title":"Sci. Rep."},{"key":"2023120103434977500_CIT0006","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1136\/annrheumdis-2019-215743","article-title":"Metagenome-wide association study of gut microbiome revealed novel aetiology of rheumatoid arthritis in the Japanese population","volume":"79","author":"Kishikawa","year":"2020","journal-title":"Ann. Rheum. 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