{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:27:36Z","timestamp":1760146056699,"version":"build-2065373602"},"reference-count":80,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Kansas (KU), via a CTSA grant from NCATS awarded to the University of Kansas for Frontiers: University of Kansas Clinical and Translational Science Institute","award":["KL2TR002367","P20GM130423","R01HD089928"],"award-info":[{"award-number":["KL2TR002367","P20GM130423","R01HD089928"]}]},{"name":"Kansas Institute of Precision Medicine Centers of Bio-medical Research Excellence grant from NIGMS awarded to the University of Kansas Medical Center","award":["KL2TR002367","P20GM130423","R01HD089928"],"award-info":[{"award-number":["KL2TR002367","P20GM130423","R01HD089928"]}]},{"name":"KU Provost","award":["KL2TR002367","P20GM130423","R01HD089928"],"award-info":[{"award-number":["KL2TR002367","P20GM130423","R01HD089928"]}]},{"name":"KU Vice Chancellor for Research and Graduate Studies","award":["KL2TR002367","P20GM130423","R01HD089928"],"award-info":[{"award-number":["KL2TR002367","P20GM130423","R01HD089928"]}]},{"name":"University of Kansas Medical Center (KUMC) Vice Chancellor for Research","award":["KL2TR002367","P20GM130423","R01HD089928"],"award-info":[{"award-number":["KL2TR002367","P20GM130423","R01HD089928"]}]},{"name":"Rheumatology Research Foundation Rheumatology Investigator Award and R Bridge Award (PI Mara Becker) as well as National Institute of Child Health and Human Development","award":["KL2TR002367","P20GM130423","R01HD089928"],"award-info":[{"award-number":["KL2TR002367","P20GM130423","R01HD089928"]}]},{"name":"Children\u2019s Mercy Kansas City (CMKC) and through a philanthropic donation to CMKC from Emily and Todd Novikoff","award":["KL2TR002367","P20GM130423","R01HD089928"],"award-info":[{"award-number":["KL2TR002367","P20GM130423","R01HD089928"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Identification of disease and therapeutic biomarkers remains a significant challenge in the early diagnosis and effective treatment of juvenile idiopathic arthritis (JIA). In this study, plasma metabolomic profiling was conducted to identify disease-related metabolic biomarkers associated with JIA. Plasma samples from treatment-na\u00efve JIA patients and non-JIA reference patients underwent global metabolomic profiling across discovery (60 JIA, 60 non-JIA) and replication (49 JIA, 38 non-JIA) cohorts. Univariate analysis identified significant metabolites (q-value \u2264 0.05), followed by enrichment analysis using ChemRICH and metabolic network mapping with MetaMapp and Cytoscape. Receiver operating characteristic (ROC) analysis determined the top discriminating biomarkers based on area under the curve (AUC) values. A total of over 800 metabolites were measured, consisting of 714 known and 155 unknown compounds. In the discovery cohort, 587 metabolites were significantly altered in JIA patients compared with the reference population (q &lt; 0.05). In the replication cohort, 288 metabolites were significantly altered, with 78 overlapping metabolites demonstrating the same directional change in both cohorts. JIA was associated with a notable increase in plasma levels of sphingosine metabolites and fatty acid ethanolamides and decreased plasma levels of sarcosine, iminodiacetate, and the unknown metabolite X-12462. Chemical enrichment analysis identified cycloparaffins in the form of naproxen and its metabolites, unsaturated lysophospholipids, saturated phosphatidylcholines, sphingomyelins, ethanolamines, and saturated ceramides as the top discriminating biochemical clusters. ROC curve analysis identified 11 metabolites classified as highly discriminatory based on an AUC &gt; 0.90, with the top discriminating metabolite being sphinganine-1-phosphate (AUC = 0.98). This study identifies specific metabolic changes in JIA, particularly within sphingosine metabolism, through both discovery and replication cohorts. Plasma metabolomic profiling shows promise in pinpointing JIA-specific biomarkers, differentiating them from those in healthy controls and Crohn\u2019s disease, which may improve diagnosis and treatment.<\/jats:p>","DOI":"10.3390\/metabo14090499","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T11:36:37Z","timestamp":1726486597000},"page":"499","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8513-673X","authenticated-orcid":false,"given":"Amar","family":"Kumar","sequence":"first","affiliation":[{"name":"Center for Computational Biology, University of Kansas, Lawrence, KS 66047, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1947-6194","authenticated-orcid":false,"given":"Joshua","family":"Tatarian","sequence":"additional","affiliation":[{"name":"University of Kansas School of Medicine, Kansas City, KS 66160, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Shakhnovich","sequence":"additional","affiliation":[{"name":"Ironwood Pharmaceuticals, Boston, MA 02110, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7628-6007","authenticated-orcid":false,"given":"Rachel L.","family":"Chevalier","sequence":"additional","affiliation":[{"name":"University of Missouri-Kansas City School of Medicine & Children\u2019s Mercy Kansas City, Kansas City, MO 64108, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Sudman","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1604-0130","authenticated-orcid":false,"given":"Daniel J.","family":"Lovell","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan D.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1088-2015","authenticated-orcid":false,"given":"Mara L.","family":"Becker","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Pediatrics, Duke University School of Medicine, Durham, NC 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3834-4672","authenticated-orcid":false,"given":"Ryan S.","family":"Funk","sequence":"additional","affiliation":[{"name":"Center for Computational Biology, University of Kansas, Lawrence, KS 66047, USA"},{"name":"University of Kansas School of Medicine, Kansas City, KS 66160, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"ref_1","first-page":"e5131","article-title":"The utility and experience with disease biomarkers in juvenile onset arthritis vs. adult onset arthritis","volume":"11","author":"Patwardhan","year":"2019","journal-title":"Cureus"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/s12969-021-00650-x","article-title":"Epidemiology and demographics of juvenile idiopathic arthritis in Africa and Middle East","volume":"19","author":"Bouayed","year":"2021","journal-title":"Pediatr. 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