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Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis
KUMAR, AMAR Tatarian, Joshua Shakhnovich, Valentina Chevalier, Rachel Sudman, Marc Lovell, Daniel Thompson, Susan Becker, Mara Funk, Ryan
KUMAR, AMAR
Tatarian, Joshua
Shakhnovich, Valentina
Chevalier, Rachel
Sudman, Marc
Lovell, Daniel
Thompson, Susan
Becker, Mara
Funk, Ryan
Abstract
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-naïve 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 ≤ 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 < 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 > 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’s disease, which may improve diagnosis and treatment.</jats:p>
Description
A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.
Date
2024-9-16
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MDPI AG
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Research Projects
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Keywords
autoimmune disease, juvenile idiopathic arthritis, metabolomics, biomarkers, disease-modifying antirheumatic drugs
Citation
Kumar, A.; Tatarian, J.; Shakhnovich, V.; Chevalier, R.L.; Sudman, M.; Lovell, D.J.; Thompson, S.D.; Becker, M.L.; Funk, R.S. Identification of Plasma Metabolomic Biomarkers of Juvenile Idiopathic Arthritis. Metabolites 2024, 14, 499. https://doi.org/10.3390/metabo14090499