{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T15:25:18Z","timestamp":1785857118273,"version":"3.56.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,12,17]],"date-time":"2020-12-17T00:00:00Z","timestamp":1608163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p><jats:bold>Objectives:<\/jats:bold> Interstitial lung disease (ILD) is an extra-articular manifestation in rheumatoid arthritis (RA), detected in 10.7% of patients, and causing a poor prognosis. Hence, biomarkers for ILD are urgently required in RA. Low molecular weight metabolites can be assessed by metabolomic analyses, and although these have been conducted in RA and in idiopathic pulmonary fibrosis, few have been carried out for ILD in the context of RA. Therefore, we analyzed serum metabolomic profiles of ILD in RA to identify novel biomarkers.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Serum samples from 100 RA patients with ILD and 100 matched RA patients without chronic lung disease (CLD) were collected. These samples were subjected to metabolomic analyses using capillary electrophoresis time-of-flight mass spectrometry.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A total of 299 metabolites were detected in the metabolomic analysis. By univariate analysis, serum levels of decanoic acid and morpholine were lower in RA with ILD (false discovery rate <jats:italic>Q<\/jats:italic> = 1.87 \u00d7 10<jats:sup>\u221211<\/jats:sup> and 7.09 \u00d7 10<jats:sup>\u22126<\/jats:sup>, respectively), and glycerol was higher (<jats:italic>Q<\/jats:italic> = 1.20 \u00d7 10<jats:sup>\u22126<\/jats:sup>), relative to RA without CLD. Serum levels of these metabolites in RA with usual interstitial pneumonia or RA with non-specific interstitial pneumonia were also altered. The partial least squares-discriminant analysis model generated from these three metabolites could successfully discriminate ILD in RA (area under the curve: 0.919, 95% confidence interval: 0.867\u20130.968, sensitivity 0.880, specificity 0.780).<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> Serum levels of some metabolites were significantly different in RA with ILD compared with RA without CLD. It is concluded that metabolomic profiling will be useful for discovering candidate screening biomarkers for ILD in RA.<\/jats:p>","DOI":"10.3389\/fmed.2020.599794","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T21:49:47Z","timestamp":1610056187000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Serum Metabolomic Profiling in Rheumatoid Arthritis Patients With Interstitial Lung Disease: A Case\u2013Control Study"],"prefix":"10.3389","volume":"7","author":[{"given":"Hiroshi","family":"Furukawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shomi","family":"Oka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Shimada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Okamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Komiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Saisho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norie","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Katayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoshi","family":"Fukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoshi","family":"Migita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeto","family":"Tohma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e33133","DOI":"10.1371\/journal.pone.0033133","article-title":"Association of human leukocyte antigen with interstitial lung disease in rheumatoid arthritis: a protective role for shared epitope","volume":"7","author":"Furukawa","year":"2012","journal-title":"PLoS ONE."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1483","DOI":"10.1093\/rheumatology\/keq035","article-title":"Interstitial lung disease has a poor prognosis in rheumatoid arthritis: results from an inception cohort","volume":"49","author":"Koduri","year":"2010","journal-title":"Rheumatology."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1000064","DOI":"10.4172\/1745-7580.1000064","article-title":"Plasma amino acid profiles in collagen disease patients with interstitial lung disease","volume":"9","author":"Furukawa","year":"2013","journal-title":"Immunome Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e40459","DOI":"10.1371\/journal.pone.0040459","article-title":"A novel serum metabolomics-based diagnostic approach for colorectal cancer","volume":"7","author":"Nishiumi","year":"2012","journal-title":"PLoS ONE."},{"key":"B5","doi-asserted-by":"publisher","first-page":"827","DOI":"10.3390\/cells9040827","article-title":"Circulating pro- and anti-inflammatory metabolites and its potential role in rheumatoid arthritis pathogenesis","volume":"9","author":"Coras","year":"2020","journal-title":"Cells."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e000183","DOI":"10.1136\/bmjresp-2017-000183","article-title":"Metabolic heterogeneity of idiopathic pulmonary fibrosis: a metabolomic study","volume":"4","author":"Zhao","year":"2017","journal-title":"BMJ Open Respir Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1717","DOI":"10.1021\/acs.jproteome.6b00156","article-title":"Metabolic profiling regarding pathogenesis of idiopathic pulmonary fibrosis","volume":"15","author":"Kang","year":"2016","journal-title":"J Proteome Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s12931-018-0714-2","article-title":"Serum metabolic profiling identified a distinct metabolic signature in patients with idiopathic pulmonary fibrosis - 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