Background/Purpose: The differential diagnosis of Rheumatoid Arthritis (RA) and Psoriatic arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical biomarkers. Lipid alterations have been suggested to contribute to the pathophysiological processes in the knee joint, and chronic inflammation induces significant changes in the synovium and synovial fluid (SF) lipidome. Therefore, we aimed to evaluate whether differences in the lipid profiles from synovial membrane (SM) and SF could support the differential diagnosis of these diseases.

Methods: SM samples of patients affected by RA (n=6), PsA (n=12) and control donors (n=10) were compared using Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) for spatially resolved lipid analysis. To this end, tissue sections were measured on a RapifleX MALDI-TOF/TOF instrument. Next, a targeted approach based on multiple reaction monitoring (MRM-MS) was performed to further validate the lipidomic alterations reported by MALDI-MSI between RA and PsA tissues. In this case, lipids extracted from SF (control donors (n=4), RA (n=21) and PsA (n=27)) were analyzed in a QTRAP 4000 mass spectrometer coupled with an ExpressHT™-Ultra HPLC system for the targeted analysis of 84 lipid species. Principal component analysis (PCA) and discriminant analysis (DA) were used for data interpretation.

Results: Lipid profiles of PsA and RA synovial membranes were unequivocally distinguished by MALDI-MSI followed by PCA-DA. Interestingly, several lipid species, including sphingomyelins, phosphatidylcholines (PC) and phosphatidylethanolamines (PE), presented the greatest separation power to classify RA and PsA tissue samples. On the other hand, the lipid profile of arthritic SM samples was also discriminated from control tissues. Specifically, several lysophosphatidylcholines showed the greatest discriminative capability for separating groups. The abundance of those lipid species with discriminatory potential were further compared using ANOVA. This analysis found 35 lipid species significantly different among the study groups, where most of them were significantly increased in RA and PsA compared to controls. Particularly, 11 lipids showed higher levels in PsA tissues compared with RA, including several PC and PE such as PE 34:1 and PE 36:1. The spatial distribution of these PE species was associated with areas of the sublining layer with increased vascularity and inflammatory cell infiltrates, according to MALDI-MSI images. On the other hand, RA and PsA patients were also correctly classified based on the SF levels of all quantified lipid species according to PCA and clustering analysis. Finally, we were able to validate the increased levels of PE 34:1 and PE 36:1 in the SF of PsA patients compared to RA (Figure 1).

Conclusion: Our study shows a distinct lipid profile between RA and PsA synovium and synovial fluid, and reports potential clinically useful lipid markers for the differential diagnosis of these diseases.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/distinct-lipidomic-signatures-in-synovium-and-synovial-fluid-of-patients-with-rheumatoid-arthritis-versus-psoriatic-arthritis/