Surface Antigens on Plasma Extracellular Vesicles of Cystic Fibrosis Patients Treated by Extracorporeal Photopheresis as Induction Therapy after Lung Transplantation: Preliminary Results of a Pilot Randomized Trial.

Acute rejection (AR) is common during the first year after lung transplantation (LuTx) and can trigger chronic rejection (CR), the leading cause of late morbidity and mortality of LuTx. Extracorporeal photopheresis (ECP) is a promising treatment for chronic rejection. Few studies focus on ECP as prophylactic therapy of AR and CR. Microvesicles and exosomes (i.e.extracellular vesicles EV) are released into the blood and in bronchoalveolar lavage (BAL) and their role in cell-to-cell communication has been assessed in several studies; EV have been proposed as non-invasive biomarkers to assess lung injury and monitor clinical outcome. We conduct a pilot clinical trial on 24 cystic fibrosis patients undergoing LuTx, randomly allocated in 2 parallel arms: standard immunosuppressive therapy and ECP (ECP) vs standard immunosuppressive therapy alone (CTR). EV concentration was assessed at different time points in blood and BAL in the first year after LuTx (analyzed by nanoparticle tracking analysis Nanosight NS300, Malvern). EV were analyzed for antigen expression with MACSplex bead-based assay. AR episodes and infections were recorded, as far as ECP-related adverse events. Preliminary data on the first 18 patients (9 ECP and 9 CTR) are reported ECP was well tollerated and no adverse events or AR occurred in either groups. EV presented highly polydispersed size distributions in a 50-1000 nm range. The expression of EV-associated markers CD63, CD9 and CD81 was detected. Upregulation of platelets (CD62p; p<0.05 by t-test), lymphocytes (CD3, CD24) markers and integrins (CD29, CD49e) was observed in ECP-treated patient compared to the control group. The underlying mechanism of ECP remains unresolved. The identification of specific EV antigen signatures may represent a promising approach to better understand the immunomodulatory effects of ECP, both at molecular and cellular level. [ABSTRACT FROM AUTHOR]