Background/Purpose: Metabolomic and lipidomic pathways serve as key sensors and effectors of genetic, epigenetic, and environmental factors that shape the development and function of the immune system. Current research in humans and animal models is using these techniques to characterize patterns that may predispose to subtypes of disease and response to treatment. Metabolomic and lipidomic analysis have not been done in pediatric rheumatic diseases such as JIA. Based on studies in rheumatoid arthritis and its “lipid paradox,” we decided to evaluate the synovial fluid of 3 patients with oligoarticular JIA naïve to treatment.

Methods: All patients had joint aspiration followed by intraarticular steroid injection. Lipids were extracted from each synovial fluid sample according to published protocol and analyzed by ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) on a Thermo Vanquish UHPLC system coupled to a Thermo Q-Exactive Orbitrap mass spectrometer.

Lipids were identified and integrated using LipidMatch software. Peak areas were normalized using the appropriate internal standards based on lipid class or chromatographic retention time. Relative-quantitative data were processed by principal component analysis (PCA) and one-way analysis of variance (ANOVA) with Fisher’s LSD post-hoc test using MetaboAnalyst software, statistical significance was inferred at p < 0.05.

Results: There were 471 lipid molecules identified in these samples. Of these, 341 appear to be significantly different between the 3 patients (p-value < 0.05), using “Anova_PostHoc” sorted by p-value. The lipids found in the largest amount included acyl-carnitines, ceramics, triacylglycerols, and phospholipids. 

Conclusion: The biologic significance of these individual lipid molecules to JIA subtype and status is currently being analyzed, as are the metabolomic results.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/lipidomic-profiles-of-synovial-fluid-from-patients-with-oligoarticular-juvenile-idiopathic-arthritis-naive-to-treatment/