Abstract
IntroductionPsoriatic arthritis (PsA), an inflammatory arthritis that develops in individuals with psoriasis, is associated with reduced quality of life. Identifying biomarkers associated with development of PsA as well as with PsA disease activity may help management of psoriatic disease.ObjectivesTo use metabolomic fingerprinting to determine potential candidate markers of disease conversion (psoriasis to PsA) and/or PsA activity.MethodsA novel sample preparation protocol based on solid-phase microextraction (SPME) was used to prepare serum samples obtained from: (1) individuals with psoriasis, some of whom develop psoriatic arthritis (n = 20); (2) individuals with varying PsA activity (mild, moderate, severe; n = 10 each) and (3) healthy controls (n = 10). Metabolomic fingerprinting of the obtained extracts was performed using reversed-phase liquid chromatography coupled to high resolution mass spectrometry.ResultsPsoriasis patients who developed PsA had similar metabolomic profiles to patients with mild PsA and were also indistinguishable from patients with psoriasis who did not develop PsA. Elevated levels of selected long-chain fatty acids (e.g., 3-hydroxytetradecanedioic acid) that are associated with dysregulation of fatty acid metabolism, were observed in patients with severe PsA. In addition, 1,11-undecanedicarboxylic acid—an unusual fatty acid associated with peroxisomal disorders—was also identified as a classifier in PsA patients vs. healthy individuals. Furthermore, a number of different eicosanoids with either pro- or anti-inflammatory properties were detected solely in serum samples of patients with moderate and severe PsA.ConclusionA global metabolomics approach was employed to analyze the serum metabolome of patients with psoriasis, PsA, and healthy controls in order to examine potential differences in the biochemical profiles at a metabolite level. A closer examination of circulating metabolites may potentially provide markers of PsA activity.
Highlights
Psoriatic arthritis (PsA), an inflammatory arthritis that develops in individuals with psoriasis, is associated with reduced quality of life
25% of psoriasis patients suffer from psoriatic arthritis (PsA), which is a specific form of inflammatory arthritis that may affect peripheral and axial joints and periarticular structures, such as the entheses (Alinaghi et al, 2019)
principal component analysis (PCA) with univariate analysis was largely employed for this study as there were only n = 10 samples per group and very close inter-group association among a number of groups, which may result in overfitting and likely failure during the cross-validation of supervised models
Summary
Psoriatic arthritis (PsA), an inflammatory arthritis that develops in individuals with psoriasis, is associated with reduced quality of life. Since PsA often develops after the onset of cutaneous psoriasis, recent research has focussed on converters—psoriatic patients who develop PsA—with the aim of identifying the mechanisms of arthritis development, developing early diagnosis methods, and implementing measures for impeding the disease’s progression, as advances in these areas have the potential to improve patient care tremendously (Abji et al, 2016; Eder et al, 2016, 2017) Progress towards these goals will require identifying more quantitative biomarkers associated with psoriatic disease pathophysiology and a deeper understanding of the biochemical relevance of these markers in driving disease progression (Petronic-Rosic & Basko-Plluska, 2012)
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