Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Persistent inflammation is a characteristic of several joint diseases, including OA. It is nowadays appreciated that this could be a result of a failure to (optimally) activate inflammation resolution pathways. Therefore, we investigated the presence of specialized pro-resolving lipid mediators (SPM) and their precursors as pathway markers of the resolution process in the joint of OA patients and controls.
Methods: SF was obtained from knee OA (2 populations) and rheumatoid arthritis (RA) patients fulfilling the ACR criteria for OA and RA, respectively, and healthy controls. Lipid mediators (LMs) were determined by targeted lipidomics using liquid-chromatography mass spectrometry. Sixty different lipids including pro-inflammatory (e.g. prostaglandins, leukotrienes) and anti-inflammatory/pro-resolving LM (e.g. SPM), as well as their precursors can be detected with our technique.
Results: SF from 24 OA and 12 RA patients were first studied. Thirty-seven lipids were detected in the soluble fraction of SF, including polyunsaturated fatty acids (PUFA) and their lipoxygenase (LOX) and cyclooxygenase (COX) pathway markers in both OA and RA patients. Among these, pro-inflammatory LM such as PGE2 and thromboxane B2, as well as the pathway markers of resolution and precursors of SPM, 17-HDHA and 18-HEPE, were detected. Except for the LOX products of arachidonic acid: 15-HETE, 6-trans-LTB4 and 20-OH- LTB4, which were lower in OA than in RA SF, all other lipid mediators and PUFA were comparable between OA and RA samples. Ratios of metabolites to their precursors indicated that both pro- (e.g. LTB4) and anti-inflammatory LOX products (e.g. 17-HDHA) are more efficiently generated in RA than in OA patients, while no differences were observed in COX products. Interestingly, the SPM resolvin D2 (RvD2) could also be detected, but only in the insoluble fraction (cells and undigested matrix), indicating that the resolution pathways are activated in OA. This expands our previous publication showing activation of resolution in RA patients. To assess the efficiency of activation of resolution in OA, we have performed targeted lipidomics on total SF in an additional study with 32 OA patients and 10 healthy controls. Confirming earlier data, most LMs were also detected in this study, including the pro-inflammatory PGE2, the SPM precursors 17-HDHA and 18-HEPE, and the SPM RvD2. Additionally, we detected 18S-resolvin E3 (18S-RvE3). Remarkably, both the absolute concentrations of the SPM RvD2 and 18S-RvE3, and the ratio to their precursors, 17-HDHA and 18-HEPE, were lower in OA compared to healthy SF, indicating less efficient generation of SPM in OA compared to healthy joints. In contrast, the pro-inflammatory lipid PGE2was higher in OA than in healthy SF, indicating that the lower activation of resolution is paired by a higher inflammatory load in OA compared with healthy individuals.
Conclusion: By using a state-of-the-art technique, we show for the first time that resolution pathways are activated in OA patients. Importantly, resolution seems to be less efficiently activated than in healthy individuals, which could account for the persistent inflammation observed in OA and RA patients.
To cite this abstract in AMA style:Jonasdottir H, Brouwers H, Attur M, Kwekkeboom J, Samuels J, Strauss E, van der Linden-van der Zwaag E, Huizinga T, Kloppenburg M, Toes R, Giera M, Abramson SB, Ioan-Facsinay A. Targeted Lipidomics Reveals Incomplete Activation of Resolution Pathways in Knee Osteoarthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/targeted-lipidomics-reveals-incomplete-activation-of-resolution-pathways-in-knee-osteoarthritis/. Accessed November 28, 2020.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/targeted-lipidomics-reveals-incomplete-activation-of-resolution-pathways-in-knee-osteoarthritis/