An investigation of skin and plasma lipids in psoriasis

Abstract

The skin forms a barrier that protects the body from the environment. Skin lipids participate in barrier formation, cell signalling, inflammation and immune responses. The skin has their own characteristic array of lipids that contribute to maintaining health but, if altered, can also contribute to skin pathologies. Psoriasis is a chronic, immune condition predominantly affecting the skin. Although the cause of psoriasis skin lesions remains unknown, there is evidence to suggest the involvement of lipids. The aim of this project was to explore the cutaneous and plasma lipidomes in psoriasis patients with variable Psoriasis Area and Severity Index (PASI) who had not received systemic medication. Skin biopsies and plasma were sampled from healthy (n = 20) and psoriasis volunteers (n = 19). When possible, biopsies from psoriasis volunteers were taken from uninvolved and involved (lesional) skin. Eicosanoids and related mediators, endocannabinoids, N-acyl ethanolamines, and ceramides were measured using ultra performance liquid chromatography coupled to triple quadrupole mass spectrometer (MS) fitted with electrospray ionisation (ESI) probe. A new assay employing ultra-performance supercritical fluid chromatography coupled to quadrupole time-of-flight MS fitted with ESI was developed and optimised to measure complex lipids (glycerolipids, glycerophospholipids, sterol lipids, sphingolipids, and free fatty acids) in skin and plasma samples. No differences were observed in the dermal and epidermal lipidomes from uninvolved skin. However, in epidermis with psoriasis lesions (involved skin) increased concentrations of non-enzymatically derived eicosanoids (p = 0.042) were detected and alterations in ceramide (CER) concentrations, including decreased CER[EOH] (p = 0.0201), CER[EOS] (p = 0.0036), CER[EOP] (p = 0.0013), CER[NH] (p = 0.0208), and CER[NP] (p = 0.0058), whereas CER[NS] were increased in psoriasis lesions (p = 0.0074). These changes may be linked to hyperproliferation of keratinocytes, a known feature in psoriasis. In plasma from psoriasis patients, decreased concentrations of cholesteryl esters (CE (16:0), p < 0.001; CE (16:1), p =

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Christopher Griffiths (Supervisor) & Anna Nicolaou (Supervisor)