Advanced lipidomics approaches in arthritis research
Abstract
Recent advances in lipidomics have significantly enhanced our ability to study the role of lipids in health and disease. This dissertation integrates cutting-edge technologies, mobility spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy, to investigate lipid and lipoprotein alterations in inflammatory diseases such as rheumatoid arthritis (RA) and osteoarthritis (OA). A cross-laboratory validation study established standardized differential mobility spectrometry (DMS)-based lipidomics method and provided consensus reference values. Comparative analysis of DMS and NMR demonstrated their complementary strengths in lipid profiling, enabling more comprehensive metabolic insights.
In OA chondrocytes, lipidomic analysis revealed a deficiency in C17:0 fatty acid associated with peroxisomal dysfunction, suggesting a link between impaired lipid metabolism and cartilage degradation. Time-resolved oxylipin profiling in a mouse OA model provided dynamic insights into inflammatory pathways during disease progression. In RA patients, elevated triglycerides and VLDL were identified as predictors of poor response to abatacept therapy, supporting the potential of lipid biomarkers for personalized treatment strategies. Additionally, a newly developed LC-MS/MS method enabled precise quantification of oxidized phospholipids, offering deeper mechanistic understanding of lipid oxidation in inflammation.
Collectively, this work advances lipidomic standardization and highlights its clinical utility in biomarker discovery and precision medicine for inflammatory diseases. By bridging methodological innovation with biological insights, this research paves the way for improved diagnostics and targeted therapies.
