A simplified extracorporeal photopheresis procedure based on single high‐dose ultraviolet A light irradiation shows similar in vitro efficacy

Abstract

Background: Extracorporeal photopheresis (ECP) is one of the most widely used and effective cell-based therapies for the treatment of T-cell-mediated diseases. The patients' white blood cells (WBCs) are collected by apheresis and exposed to the photosensitizer 8-methoxypsoralen (8-MOP) and ultraviolet A (UVA) light before retransfusion. The UVA/8-MOP combination has been in use in ECP for more than 4 decades; however, whether ECP can be simplified by UVA light irradiation only has never been analyzed. Study Design and Methods: Peripheral blood mononuclear cells were treated with classical ECP or different UVA light doses only (UVA only). Treatment efficacy was investigated by apoptosis induction in WBC subsets, inhibition of T-cell proliferation, and the ability of monocytes to induce allogeneic T-cell expansion and to respond to lipopolysaccharide and interferon-γ stimulation in vitro. Results: High-dose UVA only treatment (5 J/cm 2) was as efficient as ECP to induce apoptosis within 48 hours. UVA only treatment modulated the composition of the surviving cells by improving monocyte survival and promoting CD8 + T-cell apoptosis. Both ECP and UVA only treatment inhibited anti-CD3/ anti-CD28 triggered T-cell proliferation. Interestingly, whereas ECP-treated monocytes exhibited a markedly reduced capacity to respond to stimulation and to induce allogeneic T-cell proliferation, UVA only treatment preserved monocyte functionality to some degree. Conclusions: High-dose UVA only and standard ECP showed comparable efficacy in inducing apoptosis and inhibiting direct T-cell proliferation. Hence, UVA only treatment can be a simplified alternative to ECP therapy. Furthermore, increased monocyte survival with partially preserved functionality after UVA only treatment may provide a novel method for immunoregulation.