Immune profile changes induced by extracorporeal photopheresis as prophylactic therapy in lung transplanted cystic fibrosis patients

Abstract

Abstract Chronic rejection (CR) is the leading cause of late morbidity and mortality upon lung transplantation (LuTx). Extracorporeal photopheresis (ECP) has emerged as a promising immunomodulatory prophylactic induction treatment against rejection. We performed and in-depth investigation of the immunological effects of ECP in LuTx recipients with a diagnosis of cystic fibrosis (CF). A pilot clinical trial enrolled 20 CF LuTx patients who were randomly allocated in 2 arms: standard immunosuppressive therapy alone vs. standard immunosuppressive therapy plus ECP for 3 months, beginning within 72h from LuTx. Functional activation of T and NK subpopulations as well as mRNA expression and cytokine secretion profiling were evaluated in peripheral blood and in bronchoalveolar lavage (BAL) up to 12 months after LuTx. Clinical parameters, including respiratory volumes (e.g. FEV1), rejection episodes and infections, were analyzed as well. ECP was well tolerated with no complications nor opportunistic infections. Rejection rate was comparable in the two groups Notably, a significantly better FEV1 was observed in the ECP group overtime. Treg lymphocytes and IL10-producing NKs were significantly increased, while Th17 cells were significantly reduced in the ECP group compared to the control. Cytokine profile showed that ECP reduced pro-inflammatory cytokines (e.g. IL1b, IL6) production, increasing that of anti-inflammatory cytokines (e.g. IL10, IL1RA) both in plasma and BAL ECP is associated with immune modulation resulting in improved patients’ respiratory performance. More extensive studies and longer follow-up are needed to verify if ECP-induced immune modulation will have a beneficial effect of organ rejection as well. Supported by grants from the Cystic Fibrosis Foundation