Indication-specific immunomodulatory effects of extracorporeal photopheresis: A pilot study in heart transplanted patients

J Clin Apher. 2018 Oct;33(5):591-599. doi: 10.1002/jca.21647. Epub 2018 Sep 3.

Abstract

Background: The clinical use of extracorporeal photopheresis (ECP) is based on its ability to induce cell-mediated immune tolerance towards foreign and self-antigens. Up-to-date, no clear consensus consists on how to use ECP after heart transplantation (HTx). In this pilot study, we evaluated the stimulatory effects of ECP on immune cells in HTx patients.

Methods: HTx patients received ECP therapy as prophylaxis of rejection (PRX, n = 15), to treat acute cellular rejection (ACR, n = 13) or cardiac allograft vasculopathy (CAV, n = 5). Three ECP cycles with monthly frequency were performed. Blood samples were taken before every ECP cycle and 2 months after the last ECP cycle and were analyzed for cytokines and the tolerance-inducing cell subsets regulatory T cells (Tregs ), myeloid (mDCs), and plasmacytoid dendritic cells (pDCs).

Results: While ECP treatment induced first an increase of pDCs in the CAV group (baseline: 22.0% ± 9.6%, prior third ECP cycle: 8.6% ± 3.2%, follow-up: 31.5% ± 8.4%, P = .009), no significant changes of DC subsets and Tregs were observed in the ACR- and in the PRX group. Furthermore, analysis of the immune balance showed different response profiles of pro- and anti-inflammatory cytokines among prophylactically ECP-treated patients and ECP-treated patients suffering from CAV or ACR.

Conclusions: In our pilot study, we showed different stimulatory effects of ECP on pDCs and cytokines among prophylactic and therapeutic ECP therapy after HTx. Immunological monitoring should be included in a larger clinical study of ECP treatment following HTx and to identify predictable parameters for ECP efficacy.

Keywords: acute cellular rejection; cardiac allograft vasculopathy; cytokines; dendritic cells; extracorporeal photopheresis; heart transplantation; regulatory T cells.

MeSH terms

  • Adult
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Female
  • Graft Rejection / prevention & control
  • Heart Transplantation / methods*
  • Humans
  • Immune Tolerance*
  • Male
  • Middle Aged
  • Photopheresis / methods*
  • Pilot Projects
  • T-Lymphocytes, Regulatory / cytology
  • Vascular Diseases / etiology
  • Vascular Diseases / prevention & control

Substances

  • Cytokines