Extracorporeal photopheresis induces the release of anti-inflammatory fatty acids and oxylipins and suppresses pro-inflammatory sphingosine-1-phosphate.

in Inflammation research : official journal of the European Histamine Research Society ... [et al.] by Gerhard Hagn, Ara Cho, Nina Zila, Barbara Sterniczky, Christian Jantschitsch, Dexin Dong, Andrea Bileck, Mariia Koren, Philipp Paulitschke, Thomas Mohr, Robert Knobler, Wolfgang Peter Weninger, Christopher Gerner, Verena Paulitschke

TLDR

  • The study identified novel mechanisms of extracorporeal photopheresis (ECP) by analyzing blood plasma of patients with different ECP indications.
  • The findings suggest that ECP-induced changes in lipid mediators may contribute to the anti-inflammatory effects of the treatment and may be used to support personalized medical care.

Abstract

Extracorporeal photopheresis (ECP) is a UVA-based phototherapy of whole blood and well established as a first line or combination therapy for the treatment of cutaneous T-cell lymphoma, systemic sclerosis, graft-versus-host disease and is used to control organ transplant rejection. While the proapoptotic activity on activated T-cells is evident, the clinical efficacy of this treatment also appears to be based on other yet unknown mechanisms. In this study, we aimed to identify novel mechanisms of ECP regardless of the patient's background situation. To better understand the immediate consequences of ECP, we analyzed blood plasma of patients with different ECP indications immediately before and after treatment with regard to proteins and lipid mediators. While proteome profiling identified substantial inter-individual differences in the protein composition, no significant alteration was detectable upon treatment. In contrast, several fatty acids and lipid mediators were found to be significantly altered by ECP. Remarkably, upregulated lipid mediators including polyunsaturated fatty acids, 12-HEPE and 13-OxoODE have been described to be anti-inflammatory, while the downregulated molecules sphingosine-1-phosphate (S1P) and stearic acid are potent pro-inflammatory mediators. A selective sphingosine-1-phosphate-1 receptor (S1P1) modulator AUY954, which decreases S1P1 and experimentally reduces transplant rejection in vivo, showed greater anti-proliferative activity in human lung fibroblasts from COPD patients compared to normal lung fibroblasts, confirming that this pathway may be important in ECP and its mode of action. In conclusion, we suggest that the ECP-induced changes in lipid mediators may contribute to the remarkable anti-inflammatory effects of the treatment. Depending on their lipid status, patients may benefit from novel treatment regimens combining ECP with lipid modulators. This could be used for the prevention of transplant organ rejection, the treatment of acute or chronic GvHD or transplant organ rejection and the long-term treatment of various skin diseases. This study uncovers novel mechanisms of ECP, that can be used to establish clinically relevant lipid profiles of patients to support patient stratification, predictive or prognostic purposes and thus personalized medical care in the framework of PPPM practice. A combination with S1P modulators may therefore have beneficial effects.

Overview

  • The study aimed to identify novel mechanisms of extracorporeal photopheresis (ECP) regardless of the patient's background situation.
  • The researchers analyzed blood plasma of patients with different ECP indications before and after treatment to understand the immediate consequences of ECP.
  • The primary objective of the study was to uncover novel mechanisms of ECP that could be used to support patient stratification, predictive or prognostic purposes, and personalized medical care.

Comparative Analysis & Findings

  • The study found that no significant alterations in protein composition were detectable upon treatment, but several fatty acids and lipid mediators were found to be significantly altered.
  • The upregulated lipid mediators, including polyunsaturated fatty acids, 12-HEPE, and 13-OxoODE, were described to be anti-inflammatory, while the downregulated molecules sphingosine-1-phosphate (S1P) and stearic acid were potent pro-inflammatory mediators.
  • The selective sphingosine-1-phosphate-1 receptor (S1P1) modulator AUY954 showed greater anti-proliferative activity in human lung fibroblasts from COPD patients compared to normal lung fibroblasts, confirming the importance of this pathway in ECP.

Implications and Future Directions

  • The ECP-induced changes in lipid mediators may contribute to the remarkable anti-inflammatory effects of the treatment.
  • Depending on their lipid status, patients may benefit from novel treatment regimens combining ECP with lipid modulators for the prevention of transplant organ rejection, treatment of acute or chronic GvHD or transplant organ rejection, and long-term treatment of various skin diseases.
  • The study uncovers novel mechanisms of ECP that can be used to establish clinically relevant lipid profiles of patients to support patient stratification, predictive or prognostic purposes, and personalized medical care in the framework of PPPM practice.
Read Full Article