POS0346 THE THERAPEUTIC EFFECTS OF OMEGA-6 PUFA (PINOLENIC ACID) ON THE TRANSCRIPTOMIC PROFILE OF ACTIVATED PERIPHERAL BLOOD MONONUCLEAR CELLS ISOLATED FROM HEALTHY CONTROLS AND RHEUMATOID ARTHRITIS PATIENTS
Authors: R. Takala, D. Ramji, R. Andrews, Y. Zhou, J. Burston, E. Choy
Journal: Annals of the Rheumatic Diseases (2021)

Background: Globally, Rheumatoid arthritis (RA) is the most common chronic inflammatory arthritis. EULAR recommends patient education and disease modifying anti-rheumatic drugs including advanced targeted therapies for management 1 2 . Many patients seek advice on a dietary intervention that may improve symptoms. Foods high in omega-3 polyunsaturated fatty acids (PUFAs) is one of the most common recommended based on their anti-inflammatory properties 3 4 . Previously we showed pinolenic acid (PNLA), an omega-6 (PUFAs) found in pine nuts, reduced lipid uptake, endocytosis and migration of monocyte in vitro . PNLA also reduced IL-6, TNF-α, IL-1β and PGE2 produced by lipopolysaccharide (LPS) activated PBMCs from patients with RA and healthy controls (HCs). Objectives: We hypothesis that PNLA inhibits key inflammatory processes in synovities as in diagram.1. We investigated the transcriptomic profile of PNLA treatment on LPS activated PBMCs isolated from HCs and RA patients. Methods: Adult RA patients (n=6) were recruited from the Rheumatology Department of University Hospital of Wales together with 6 HCs. Blood was collected after taking signed informed consent. PBMCs were isolated by Ficoll gradient centrifugation and pre-treated with 25 μM PNLA or vehicle and then activated with 100 ng/ml LPS. RNA was extracted followed by library construction and sequencing for whole genomic transcriptome. DEGs were analysed using DESeq2 and pathway analysis was performed using Ingenuity pathway analysis. The study was approved by the Research Ethics Committee for Wales (reference no. 12/WA/0045). Results: DEGs were selected with at least differential genes using at least 1.2* fold changes and adjusted p-value of &lt;0.05. PNLA significantly upregulates the expression of PDK4, PAI-1 (SERPINE1), FBP1, and NDRG2. These genes have important roles in metabolic pathways. Pathway analysis predicted upstream activation of nuclear receptors peroxisome proliferator-activated receptor (PPARs) involved in the anti-inflammatory process, and inhibition of NF-κB and STAT1, the major transcription factors of the pro-inflammatory cytokines TNF-α, IL-1, IL-6 and IFN-γ. Conclusion: PNLA has significant effects on the regulation of metabolic and inflammatory pathways in PBMCs from RA patients and HCs. Based on these results we demonstrate that PNLA may have beneficial anti-inflammatory effects in patients with RA References: [1]Agca R, Heslinga SC, Rollefstad S, Heslinga M, McInnes. IB, Peters MJL, Kvien, TK., Dougados, M, Radner, H, Atzeni, F. and Primdahl, J. 2017. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Annals of the rheumatic diseases , 76 (1), pp.17-28. [2]Smolen JS, Landewé RBM, Bijlsma JWJ, et al. 2019. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: updateAnnals of the Rheumatic Diseases 2020; 79:685-699. [3]Chehade L, Jaafar ZA, El Masri D, Zmerly H, Kreidieh D, Tannir H, Itani L, and El Ghoch, M. 2019. Lifestyle Modification in Rheumatoid Arthritis: Dietary and Physical Activity Recommendations Based on Evidence. Current rheumatology reviews , 15 (3), pp.209-214. [4]Marchand NE, Chiu Y-H, Yoshida K, Malspeis S, Sparks JA, Costenbader K, et al. Threshold Level for Long-term Healthy Diet Adherence to Reduce the Risk of Rheumatoid Arthritis Among Women in a Prospective Cohort Using a Marginal Structural Model Approach .: 25 . Diagram 1. Disclosure of Interests: None declared