Metabolomics investigates a broad range of small molecules, allowing researchers to understand disease-related changes downstream of the genome and proteome in response to external environmental stimuli. It is an emerging technology that holds promise in identifying biomarkers and informing the practice of precision medicine. In this review, we summarize the studies that have examined endogenous metabolites in patients with psoriasis and/or psoriatic arthritis using nuclear magnetic resonance (NMR) or mass spectrometry (MS) and were published through 26 January 2021. A standardized protocol was used for extracting data from full-text articles identified by searching OVID Medline ALL, OVID Embase, OVID Cochrane Central Register of Controlled Trials and BIOSIS Citation Index in Web of Science. Thirty-two studies were identified, investigating various sample matrices and employing a wide variety of methods for each step of the metabolomics workflow. The vast majority of studies identified metabolites, mostly amino acids and lipids that may be associated with psoriasis diagnosis and activity. Further exploration is needed to identify and validate metabolomic biomarkers that can accurately and reliably predict which psoriasis patients will develop psoriatic arthritis, differentiate psoriatic arthritis patients from patients with other inflammatory arthritides and measure psoriatic arthritis activity.
Introduction
Psoriatic 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.
Objectives
To use metabolomic fingerprinting to determine potential candidate markers of disease conversion (psoriasis to PsA) and/or PsA activity.
Methods
A 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.
Results
Psoriasis 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.
Conclusion
A 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.
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