Lung Transplantation and Extracorporeal Photopheresis as Induction Therapy in Cystic Fibrosis Patients: Immune System Profile Changes

Abstract

<h3>Purpose</h3> Acute rejection (AR), common during the first year after lung transplantation (LuTx), can trigger chronic rejection (CR), the leading cause of late morbidity and mortality of LuTx. Extracorporeal photopheresis (ECP) has emerged as a promising treatment for chronic rejection. Only few studies are focus on ECP as prophylactic therapy of AR and CR. This study aims to verify, in recipients affected by cystic fibrosis (CF), whether the induction therapy with ECP can decrease the rate of AR, in order to impact positively on CR (primary end point: survival, AR). The expected results are the reduction of AR episodes in its clinical and histopathological manifestations. <h3>Methods</h3> This is a pilot clinical trial on 20 CF lung-transplanted patients, randomize, 2 parallel arms: standard immunosuppressive therapy and ECP (ECP) vs standard immunosuppressive therapy alone (CTR). We investigated the effect of ECP by the evaluation of lymphocyte immunophenotype by multiplex essay (CD4 + and CD25 +), the cytokine profile, the leukocytes subsets (by flow cytometry) in blood and BAL at different time points. AR episodes and infections were recorded, as far as ECP-related adverse events. <h3>Results</h3> No differences were detected in terms of AR episodes. Treg cells were significantly increased in the ECP group at 3 weeks post LuTx, and this difference was more evident 1 year post LuTx . Th17 cells were diminished in the ECP group. The anti-inflammatory IL10-producing NKs were significantly increased in the ECP group. Cytokine profile, both in BAL and plasma obtained at defined time points shows that in ECP group pro-inflammatory cytokines were early reduced and anti-inflammatory cytokines were upregulated. <h3>Conclusion</h3> In FC lung transplanted patients ECP was well tolerated without increasing in opportunistic infections. Its tolerogenic effect was not pointed out in terms of AR episodes, but has been confirmed in the immunological setting of ECP patients vs control: it prevents decline in Treg and NK observed with standard immunosuppressive drugs, with higher expression of anti-inflammatory cytokines (Il10, Il1RA) and less pro-inflammatory ones (Il1beta, Il6). Its effect is more evident months after the end of ECP treatment. The schedule of ECP prophylactic treatment has to be tested in an ampler cohort in order to reach its best immunomodulatory effect.