Circulating miRNAs Implication in Mechanisms of Response to ECP Therapy in BOS

PURPOSE: Extracorporeal photopheresis (ECP) has emerged as a promising treatment after lung transplantation (LTx) and several researches data suggest slowing or cessation of disease progression after treatment. So far, few studies have explored the molecular regulation and to date no studies have addressed how specific is miRNA expression change during ECP. The aim of the study was to analyze the expression of miRNAs potentially involved ECP response after LTx, and in particular, their changes in responding and non-responding patients to this therapy. METHODS: LTx patients underwent ECP therapy by off-line methods according to internal protocols. Plasma were drawn pre-ECP and after 3 and 6 months of treatment. We include 12 patients who have undergone transplantation and developed BOS. Patients whose FEV1 declined less than 10% with respect to basal value were classified as responders. The selection of miRNAs included for the study derives from a previous research which showed miRNAs potentially involved in graft versus host disease; from which a possible involvement of miR-22-5p, miR-34a-5p, miR-148a-3p, miR-505-3p was shown. In addition, we evaluated miR-21a-5p expression levels, given its widely demonstrated involvement in literature. We quantified candidate miRNAs using by qRT-PCR. RESULTS: Among analyzed micro-RNAs not significant change was detectable for all miRNAs considered in patients with respect to controls. Furthermore, not appear to be variations in the post-treatment levels for miR-22-5p, miR-34a-5p, miR-148a-3p, miR-505-3p after 3 and 6 months. On the contrary, a significant decrease of miR-21a-5p at 6 months was documented among responders patients compared to non-responders. CONCLUSION: This study identifies miR-21a-5p as a mechanism associated to ECP suggesting that it can provide not only important clues to pathogenesis but it is also implicated in the mechanisms of response to ECP therapy in BOS.