Background/Purpose: Early diagnosis of inflammatory arthritis is associated with improved patient outcomes. However, accurate diagnosis can be challenging because of their complexity and heterogeneous nature. Synovitis is a common pathological event undergoing arthritis which causes severe histological changes in the synovium. In this work, we evaluated the lipid signature of the synovium from different forms of inflammatory arthropathies using mass spectrometry imaging, in order to identify novel biomarkers that may enable an accurate and differential diagnosis and patient classification.

Methods: Synovial membrane biopsies of patients affected by osteoarthritis (OA, n=13), rheumatoid arthritis (RA, n=6), psoriatic arthritis (PsA, n=12) and healthy controls (n=10) were compared by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Tissue sections were deposited on conductive slides and coated with different matrices for lipid extraction. Lipid measurements were acquired in duplicate on a rapifleX MALDI Tissuetyper™ time-of-flight instrument in both ion modes. On-tissue MS/MS was performed on a MALDI-enabled Orbitrap Elite to confirm the molecular identity of lipids. Principal component analysis (PCA) and discriminant analysis (DA) were employed to classify lipids specific for each disease. Statistically significant changes were established at p< 0.05.

Results: MALDI-MSI in combination with PCA-DA showed a good separation of OA patients and controls pointing out a differential lipid profile between OA and control biopsies. OA tissues showed higher lipid content in the mass/charge (m/z) range 600-800, relative to controls. OA lipid intensities were normalized to healthy tissues to determine disease-associated lipidomic profiles of synovium. This analysis showed 35 phospholipids significantly different between OA and controls. These were mainly phosphatidylcholines (PC, 30%), phosphatidylethanolamines (PE, 26%), phosphatidylinositols (PI, 26%), phosphatidylserines (PS, 14%) and lysophosphatylcholines (LPC, 6%). PCA-DA analysis displayed a clear separation between OA and highly inflammatory arthritis (PsA and RA) based on lipid profiles (Figure 1A). Particularly, PC (m/z 732.5, 760.5 and 786.5) and sphingomyelins (m/z 703.5) were significantly upregulated in OA (Figure 1B). Some of them also showed a specific spatial distribution within the tissue. For instance, PC m/z 732.5 and m/z 786.5 were localized in the lining layer of hyperplastic OA synovium (Figure 1C). In contrast, most of PE were significantly more abundant in PsA, whereas phosphatidic acids distinguished RA synovium from OA.

Conclusion: OA synovial tissues were characterized by a higher content of PCs and sphingomyelins compared to healthy controls and other inflammatory joint diseases such as PsA and RA. These molecules may have an important role in the synovitis associated with the pathogenesis of OA, and constitute relevant molecular disease classifiers for the OA diagnosis.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-of-distinct-lipidomic-profiles-in-synovial-membranes-from-inflammatory-arthritis-by-mass-spectrometry-imaging/