Differences in oxylipin profile in psoriasis versus psoriatic arthritis

Abstract

Background Oxylipins are biological lipids that have been implicated in inflammation. We previously found that certain oxylipins correlated with clinical manifestations in psoriatic arthritis (PsA) patients. Here, we compare oxylipin profiles in PsA patients and those with psoriasis (PsO) without inflammatory arthritis to identify oxylipins that associate with specific disease manifestations to better understand disease pathogenesis and identify new biomarkers. Methods Consecutive patients with PsA (who met the CASPAR classification criteria for PsA) and PsO were recruited from the Rheumatology Outpatient Clinic. A thorough clinical examination was performed, including entheseal (Leeds enthesitis index (LEI)) and joint involvement (SJC/TJC 66/68). Patients were evaluated for pain and global disease activity on a visual analog scale (VAS) ranging from 0 to 100. This was followed by disease activity scores calculation: cDAPSA (Disease Activity Index for Psoriatic Arthritis) and Psoriasis Area and Severity Index (PASI). Serum oxylipins were determined by mass spectrometry and their association with clinical characteristics (PASI/LEI and cDAPSA) was analyzed using Metaboanalyst 4.0 and R version 3.6.1. Results Twenty PsO (average age 52 [10.8], 55% males) and 19 PsA patients (average age 60.5 [11.4], 63.1% males) were included. PsO patients had an average body mass index (BMI) of 33.7 (6.84) and an average PASI of 3.8 (4.2). PsA patients had an average BMI of 31.9 (5.6), TJC of 9.3 (10.41), SJC of 3.7 (4.23), with an average cDAPSA of 23.3 (11.4). 63.1% of PsA patients had enthesitis (average LEI 2.2 [3]) and the same percentage had psoriasis (average PASI 3(5]). Sera were analyzed for oxylipin levels. PsO and PsA patients with higher PASI score (> 2.5) had significantly lower serum concentrations of pro-inflammatory oxylipins, most of them arachidonic acid derived (AA). Oxylipin profiling did not associate with cDAPSA. Interestingly, several AA-derived oxylipins (5,15 di-HETE (5S,15S-dihydroxy-6E,8Z,10Z,13E-eicosatetraenoic acid), 5-oxoETE (5-Oxo-eicosatetraenoic acid), PGE2 (prostaglandin E2), 11bPGE2 (11 beta prostaglandin D2), and LTB4 (leukotriene B4)) were significantly increased in PsA patients with enthesitis compared to those without. Conclusions The AA-derived proinflammatory oxylipins were lower in both PsO and PsA patients with higher skin scores. Joint disease activity was not associated with the concentrations of oxylipins. Yet, enthesitis was associated with an increase of AA-derived pro-inflammatory oxylipins in PsA patients. Further studies are needed to determine whether oxylipin profiling can be a good biomarker of enthesitis in PsA patients.

Dysregulation of Bile Acids, Lipids, and Nucleotides in Psoriatic Arthritis Revealed by Unbiased Profiling of Serum Metabolites

“…Elevated levels of inflammatory and antiinflammatory lipid metabolites were observed in PsP-A patients, including the docosanoid 4-HDoHE and multiple eicosanoids including 5-HETE, 12-HETE, and 12-HHTrE. It is important to note that Coras et al performed in-depth lipid profiling and reported elevated levels of many pro-and antiinflammatory eicosanoids in PsA, and elevated levels of some eicosanoids correlated with disease severity (10,15). Although our metabolomics platform was not directed toward in-depth profiling of lipids, our findings from untargeted analysis nevertheless are consistent with their results (10,15).…”

“…It is important to note that Coras et al performed in-depth lipid profiling and reported elevated levels of many pro-and antiinflammatory eicosanoids in PsA, and elevated levels of some eicosanoids correlated with disease severity (10,15). Although our metabolomics platform was not directed toward in-depth profiling of lipids, our findings from untargeted analysis nevertheless are consistent with their results (10,15). The increase of proinflammatory lipid metabolites such as leukotriene B4 and leukotriene B5 are indicative of systematic inflammation in PsA patients, while elevated levels of antiinflammatory eicosanoids such as 5-HETE and 12-HETE likely result from inflammation-triggered responses to minimize tissue damage.…”

Metabolomic analysis in spondyloarthritis: A systematic review

“…On the other hand, the demand of proinflammatory (ω6-PUFAs) and anti-inflammatory (ω3-PUFAs) mediators is increased to perpetuate the immunometabolic response. Arachidonic acid, a representative ω6-PUFA, is correlated with disease activity in SpA (Pompeia et al, 2003;Von Hegedus et al, 2017;Coras et al, 2019bCoras et al, , 2021. Conversely, ω3-PUFAs have been proposed to act as anti-inflammatory mediators and potentially affect innate and adaptive immune function, as well as the production of cytokines and reactive oxygen species (Gheita et al, 2012;Miles and Calder, 2012).…”

Serum Oxylipin Profiles Identify Potential Biomarkers in Patients with Acute Aortic Dissection

“…Oxylipins play an important role in inflammatory pathways in arthritis, obesity, atherosclerosis and other fields [ 42 , 43 , 44 ]. Inflammation is one of the key mechanisms of AD.…”