Abstract

Psoriasis is a common and chronic inflammatory skin disease that is complicated by gene–environment interactions. Although genomic, transcriptomic, and proteomic analyses have been performed to investigate the pathogenesis of psoriasis, the role of metabolites in psoriasis, particularly of lipids, remains unclear. Lipids not only comprise the bulk of the cellular membrane bilayers but also regulate a variety of biological processes such as cell proliferation, apoptosis, immunity, angiogenesis, and inflammation. In this study, an untargeted lipidomics approach was used to study the lipid profiles in psoriasis and to identify lipid metabolite signatures for psoriasis through ultra-performance liquid chromatography-tandem quadrupole mass spectrometry. Plasma samples from 90 participants (45 healthy and 45 psoriasis patients) were collected and analyzed. Statistical analysis was applied to find different metabolites between the disease and healthy groups. In addition, enzyme-linked immunosorbent assay was performed to validate differentially expressed lipids in psoriatic patient plasma. Finally, we identified differential expression of several lipids including lysophosphatidic acid (LPA), lysophosphatidylcholine (LysoPC), phosphatidylinositol (PI), phosphatidylcholine (PC), and phosphatidic acid (PA); among these metabolites, LPA, LysoPC, and PA were significantly increased, while PC and PI were down-regulated in psoriasis patients. We found that elements of glycerophospholipid metabolism such as LPA, LysoPC, PA, PI, and PC were significantly altered in the plasma of psoriatic patients; this study characterizes the circulating lipids in psoriatic patients and provides novel insight into the role of lipids in psoriasis.

Highlights

  • Psoriasis is a common and chronic inflammatory skin disease [1, 2]

  • We found that elements of glycerophospholipid metabolism such as lysophosphatidic acid (LPA), LysoPC, phosphatidic acid (PA), protease inhibitors (PIs), and PC were significantly altered in the plasma of psoriatic patients; this study characterizes the circulating lipids in psoriatic patients and provides novel insight into the role of lipids in psoriasis

  • Lipid dysregulation is a pathogenic characteristic of many diseases, including cardiovascular diseases, hypertension, diabetes, and Alzheimer’s disease; some dysregulated lipids may act as important biomarkers [27,28,29]

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Summary

Background

Psoriasis is a common and chronic inflammatory skin disease [1, 2]. Histologically, psoriasis is defined by epidermal hyperplasia, keratinocyte differentiation with regenerative maturation, prominent blood vessels in the dermis, and inflammatory leukocyte infiltration. Based on the PLS-DA analysis and Q-value evaluation, the criteria of VIP ≥ 1 and Q-value < 0.05 were set to discover significant differential features (339 in positive mode and 188 in negative mode) between the psoriasis group and healthy subjects. After applying the criteria above, there were no differential ions between the mild and moderate-severe groups (data not shown) This revealed that there were no significant differences in lipids among subgroups. Because the PA identification rate in the lipid profiling was relatively low, we did not get any differential PAs. considering that the LPCs and PCs have important relationships with LPAs and PAs [24], we performed an ELISA to examine LPA and PA abundance in plasma from psoriasis and healthy patients.

Discussion
Methods
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Findings
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