Proteomic plasma profile of psoriatic patients

Abstract

Background: Psoriasis is a chronic, immune-mediated inflammatory skin disease with severe consequences for the whole organism. The lack of complete knowledge of the main factors predisposing an individual to the appearance of psoriatic lesions, has recently led to the search for modifications in biochemical pathways participating in the development of this disease. We therefore aimed to investigate changes in the plasma proteomic profile of patients with psoriasis.

Material and methods: A proteomics approach was used to analyze the expression of proteins in plasma from psoriatic patients and healthy controls (sex- and age-matched individuals). The analysis was performed using gel electrophoresis, followed by nanoflow LC-MS/MS using a Q-Exactive OrbiTrap mass spectrometer.

Results: Proteomic data indicated a significant decrease in the level of proteins involved in lipid metabolism, such as apolipoprotein M, and proteins involved in the management of vitamin D levels in psoriatic patients' plasma. These changes were accompanied by the expression of proteins involved in immune response and signal transduction. This was particularly evident by the level of transcriptional factors, including AT motif binding factor 1, which regulates excessive cellular proliferation and differentiation. It was also suggested that psoriasis development was associated with increased expression of proteins directly involved in signaling molecule secretion [biotinidase and BAI1-associated protein 3]. In addition, the lipid peroxidation product - 4-hydroxynonenal (4-HNE) generates higher level of adducts with proteins in the plasma of psoriatic patients. Moreover, plasma proteins from healthy subjects creating with 4-HNE adducts were mainly characterized as structural, while in the plasma of psoriatic patients, increased levels of 4-HNE-protein adducts with catalytic activity were observed.

Conclusion: The results presented herein confirm the current knowledge about the profile of proteins responsible for the immune response and management of vitamin D in the plasma of psoriatic patients. However, several new proteins were also identified, which are involved in signal transduction and lipid metabolism as well as catalytic activity. The expression or structure of these proteins was shown to change through the course of the development of psoriasis. This knowledge may help contribute to the design of more specific pharmacotherapy.

Keywords: 4-HNE-protein adducts; Plasma; Proteome; Psoriasis.