The plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory status
Abstract Background Juvenile idiopathic arthritis (JIA) is challenging to classify and effectively monitor due to the lack of disease- and subtype-specific biomarkers. A robust molecular signature that tracks with specific JIA features over time is urgently required, and targeted plasma metabolomics...
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BMC
2024-12-01
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| Series: | Pediatric Rheumatology Online Journal |
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| Online Access: | https://doi.org/10.1186/s12969-024-01041-8 |
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| author | Jooa Kwon Melanie R. Neeland Justine A. Ellis Jane Munro Richard Saffery Boris Novakovic Toby Mansell |
| author_facet | Jooa Kwon Melanie R. Neeland Justine A. Ellis Jane Munro Richard Saffery Boris Novakovic Toby Mansell |
| author_sort | Jooa Kwon |
| collection | DOAJ |
| description | Abstract Background Juvenile idiopathic arthritis (JIA) is challenging to classify and effectively monitor due to the lack of disease- and subtype-specific biomarkers. A robust molecular signature that tracks with specific JIA features over time is urgently required, and targeted plasma metabolomics may reveal such a signature. The primary aim of this study was to characterise the differences in the plasma metabolome between JIA patients and non-JIA controls and identify specific markers of JIA subtype. We also assessed the extent to which these signatures are due to underlying inflammation as assessed by glycoprotein acetyls (GlycA) and high-sensitivity C-Reactive Protein (hsCRP) levels. Methods Targeted nuclear magnetic resonance (NMR) metabolomic profiles of plasma of 72 children with JIA and 18 controls were assessed cross-sectionally. Associations between 71 metabolomic biomarkers and JIA, JIA subtype, disease activity status, and inflammation markers (GlycA and hsCRP) were assessed using multivariable linear regression models. Results JIA was associated with higher GlycA (mean difference = 0.93 standard deviations, 95% confidence interval = [0.370, 1.494], P adj = 0.039) and docosahexaenoic acid (1.06, [0.51, 1.60], P adj = 0.021), and lower acetate (-0.92, [-1.43, -0.41], P adj = 0.024) relative to controls. This variation was largely driven by systemic JIA (sJIA), with 24 of 71 total biomarkers significantly different (P adj <0.05) relative to controls. There were no specific differences identified in oligoarticular (oJIA) or polyarticular (rheumatoid factor positive or negative) JIA relative to controls. Despite being generally highly correlated with hsCRP (r > 0.70), GlycA, but not hsCRP, was positively associated with active disease in sJIA (0.22, [-0.40, -0.04], P adj = 0.018), and 6 of 24 sJIA-associated markers were associated with GlycA levels. Only 1 sJIA-associated biomarker, histidine, was associated with hsCRP levels. Conclusion Differences in the plasma NMR metabolomic profiles are apparent in children with sJIA, but not other JIA subtypes, relative to non-JIA controls. These findings suggest a potential utility for classifying and monitoring JIA through metabolomic profiling, with chronic inflammation, measured by GlycA, potentially playing a role in at least some of these metabolomic differences. |
| format | Article |
| id | doaj-art-8bbb87a97d3e46f3a3b2cd34a7aa6195 |
| institution | Kabale University |
| issn | 1546-0096 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Pediatric Rheumatology Online Journal |
| spelling | doaj-art-8bbb87a97d3e46f3a3b2cd34a7aa61952025-01-05T12:11:13ZengBMCPediatric Rheumatology Online Journal1546-00962024-12-0122111210.1186/s12969-024-01041-8The plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory statusJooa Kwon0Melanie R. Neeland1Justine A. Ellis2Jane Munro3Richard Saffery4Boris Novakovic5Toby Mansell6Infection, Immunity and Global Health Theme, Murdoch Children’s Research InstituteInfection, Immunity and Global Health Theme, Murdoch Children’s Research InstituteNorthern Health Research Development and Governance UnitInfection, Immunity and Global Health Theme, Murdoch Children’s Research InstituteInfection, Immunity and Global Health Theme, Murdoch Children’s Research InstituteInfection, Immunity and Global Health Theme, Murdoch Children’s Research InstituteInfection, Immunity and Global Health Theme, Murdoch Children’s Research InstituteAbstract Background Juvenile idiopathic arthritis (JIA) is challenging to classify and effectively monitor due to the lack of disease- and subtype-specific biomarkers. A robust molecular signature that tracks with specific JIA features over time is urgently required, and targeted plasma metabolomics may reveal such a signature. The primary aim of this study was to characterise the differences in the plasma metabolome between JIA patients and non-JIA controls and identify specific markers of JIA subtype. We also assessed the extent to which these signatures are due to underlying inflammation as assessed by glycoprotein acetyls (GlycA) and high-sensitivity C-Reactive Protein (hsCRP) levels. Methods Targeted nuclear magnetic resonance (NMR) metabolomic profiles of plasma of 72 children with JIA and 18 controls were assessed cross-sectionally. Associations between 71 metabolomic biomarkers and JIA, JIA subtype, disease activity status, and inflammation markers (GlycA and hsCRP) were assessed using multivariable linear regression models. Results JIA was associated with higher GlycA (mean difference = 0.93 standard deviations, 95% confidence interval = [0.370, 1.494], P adj = 0.039) and docosahexaenoic acid (1.06, [0.51, 1.60], P adj = 0.021), and lower acetate (-0.92, [-1.43, -0.41], P adj = 0.024) relative to controls. This variation was largely driven by systemic JIA (sJIA), with 24 of 71 total biomarkers significantly different (P adj <0.05) relative to controls. There were no specific differences identified in oligoarticular (oJIA) or polyarticular (rheumatoid factor positive or negative) JIA relative to controls. Despite being generally highly correlated with hsCRP (r > 0.70), GlycA, but not hsCRP, was positively associated with active disease in sJIA (0.22, [-0.40, -0.04], P adj = 0.018), and 6 of 24 sJIA-associated markers were associated with GlycA levels. Only 1 sJIA-associated biomarker, histidine, was associated with hsCRP levels. Conclusion Differences in the plasma NMR metabolomic profiles are apparent in children with sJIA, but not other JIA subtypes, relative to non-JIA controls. These findings suggest a potential utility for classifying and monitoring JIA through metabolomic profiling, with chronic inflammation, measured by GlycA, potentially playing a role in at least some of these metabolomic differences.https://doi.org/10.1186/s12969-024-01041-8Juvenile idiopathic arthritisJIASystemic JIAPolyarticularRheumatoid factorNMR metabolomics |
| spellingShingle | Jooa Kwon Melanie R. Neeland Justine A. Ellis Jane Munro Richard Saffery Boris Novakovic Toby Mansell The plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory status Pediatric Rheumatology Online Journal Juvenile idiopathic arthritis JIA Systemic JIA Polyarticular Rheumatoid factor NMR metabolomics |
| title | The plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory status |
| title_full | The plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory status |
| title_fullStr | The plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory status |
| title_full_unstemmed | The plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory status |
| title_short | The plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory status |
| title_sort | plasma metabolome of juvenile idiopathic arthritis varies according to subtype and underlying inflammatory status |
| topic | Juvenile idiopathic arthritis JIA Systemic JIA Polyarticular Rheumatoid factor NMR metabolomics |
| url | https://doi.org/10.1186/s12969-024-01041-8 |
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