Roxana Coras1,2, Arthur Kavanaugh1, Tristan Boyd1, Quyen Huynh1, Brian Pedersen1, Aaron M Armando1,3, Signe Dahlberg-Wright1,3, Sara Marsal4, Mohit Jain1,3, Taraneh Paravar5, Oswald Quehenberger1,3, Monica Guma6,7,8. 1. Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA. 2. Department of Medicine, Autonomous University of Barcelona, Plaça Cívica, Bellaterra, 08193, Barcelona, Spain. 3. Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA. 4. Rheumatology Department, Vall Hebron Research Institute, Autonomous University of Barcelona, Passeig Vall d'Hebron, 119-129, Barcelona, 08035, Spain. 5. Department of Dermatology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA. 6. Department of Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Drive, San Diego, CA, 92093, USA. mguma@ucsd.edu. 7. Department of Medicine, Autonomous University of Barcelona, Plaça Cívica, Bellaterra, 08193, Barcelona, Spain. mguma@ucsd.edu. 8. Division of Rheumatology, Allergy and Immunology, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA, 92093-0656, USA. mguma@ucsd.edu.
Abstract
INTRODUCTION: Eicosanoids are biological lipids that serve as both activators and suppressors of inflammation. Eicosanoid pathways are implicated in synovitis and joint destruction in inflammatory arthritis, yet they might also have a protective function, underscoring the need for a comprehensive understanding of how eicosanoid pathways might be imbalanced. Until recently, sensitive and scalable methods for detecting and quantifying a high number of eicosanoids have not been available. OBJECTIVE: Here, we intend to describe a detailed eicosanoid profiling in patients with psoriatic arthritis (PsA) and evaluate correlations with parameters of disease activity. METHODS: Forty-one patients with PsA, all of whom satisfied the CASPAR classification criteria for PsA, were studied. Outcomes reflecting the activity of peripheral arthritis as well as skin psoriasis, Disease Activity Score (DAS)28, Clinical Disease Index (CDAI) and Body Surface Area (BSA) were assessed. Serum eicosanoids were determined by LC-MS, and the correlation between metabolite levels and disease scores was evaluated. RESULTS: Sixty-six eicosanoids were identified by reverse-phase LC/MS. Certain eicosanoids species including several pro-inflammatory eicosanoids such as PGE2, HXB3 or 6,15-dk,dh,PGF1a correlated with joint disease score. Several eicosapentaenoic acid (EPA)-derived eicosanoids, which associate with anti-inflammatory properties, such as 11-HEPE, 12-HEPE and 15-HEPE, correlated with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) as well. Of interest, resolvin D1, a DHA-derived anti-inflammatory eicosanoid, was down-regulated in patients with high disease activity. CONCLUSION: Both pro- and anti-inflammatory eicosanoids were associated with joint disease score, potentially representing pathways of harm as well as benefit. Further studies are needed to determine whether these eicosanoid species might also play a role in the pathogenesis of joint inflammation in PsA.
INTRODUCTION:Eicosanoids are biological lipids that serve as both activators and suppressors of inflammation. Eicosanoid pathways are implicated in synovitis and joint destruction in inflammatory arthritis, yet they might also have a protective function, underscoring the need for a comprehensive understanding of how eicosanoid pathways might be imbalanced. Until recently, sensitive and scalable methods for detecting and quantifying a high number of eicosanoids have not been available. OBJECTIVE: Here, we intend to describe a detailed eicosanoid profiling in patients with psoriatic arthritis (PsA) and evaluate correlations with parameters of disease activity. METHODS: Forty-one patients with PsA, all of whom satisfied the CASPAR classification criteria for PsA, were studied. Outcomes reflecting the activity of peripheral arthritis as well as skin psoriasis, Disease Activity Score (DAS)28, Clinical Disease Index (CDAI) and Body Surface Area (BSA) were assessed. Serum eicosanoids were determined by LC-MS, and the correlation between metabolite levels and disease scores was evaluated. RESULTS: Sixty-six eicosanoids were identified by reverse-phase LC/MS. Certain eicosanoids species including several pro-inflammatory eicosanoids such as PGE2, HXB3 or 6,15-dk,dh,PGF1a correlated with joint disease score. Several eicosapentaenoic acid (EPA)-derived eicosanoids, which associate with anti-inflammatory properties, such as 11-HEPE, 12-HEPE and 15-HEPE, correlated with DAS28 (Disease Activity Score) and CDAI (Clinical Disease Activity Index) as well. Of interest, resolvin D1, a DHA-derived anti-inflammatory eicosanoid, was down-regulated in patients with high disease activity. CONCLUSION: Both pro- and anti-inflammatory eicosanoids were associated with joint disease score, potentially representing pathways of harm as well as benefit. Further studies are needed to determine whether these eicosanoid species might also play a role in the pathogenesis of joint inflammation in PsA.
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