1034-LBO: Differential microRNA expression profiling in lung allograft recipients who develop donor specific antibody and Bronchiolitis Obliterans Syndrome

Aim Bronchiolitis Obliterans Syndrome (BOS), clinically diagnosed as chronic rejection, has remained a major setback following lung transplantation (LT). However, its pathogenesis is poorly understood and no predictive biomarkers have been identified. Expression of microRNA (miRNA) in blood is deregulated in physiopathological conditions including immunological disorders. Methods In this study, we hypothesized that miRNA profiles from peripheral blood mononuclear cells (PBMCs) in LT recipients (LTxR) could identify patients at risk of BOS. MiRNA expression profiling was performed using TaqMan Human MicroRNA Array in PBMCs collected from three groups of LTxR: 10 stable, 10 who developed DSA and 10 who developed BOS. Results There were 98 miRNAs upregulated in LTxR with BOS compared to that of stable transplants (relative fold > 2.5); and 32 miRNAs downregulated with BOS (relative fold > 2.5). In addition, we found that there were 16 miRNAs upregulated (including miR-99a, miR-147, and miR-124 ∗ ) with BOS compared to that of DSA; and 5 miRNAs downregulated (including miR-34b, miR-363 ∗ , and miR-155 ∗ ) in BOS compared to DSA, indicating that these miRNAs may play a role in BOS with DSA. We validated those differential miRNAs in independent PBMCs and broncheoalveolar lavage cells using Taqman real-time PCR. In addition we focused on one miRNA, miR-99a, which caused upregulation of 2.8-fold in LTxR with BOS compared to that of DSA. Bioinformatics prediction indicated that miR-99a can mediate gene-expression regulation of TNIK (TRAF2 and NCK interacting kinase) and TRAF4 (TNF receptor-associated factor 4), which were involved in regulating NF- κ B signaling pathway. Conclusions In conclusion our results demonstrate that differential miRNA expression profile has the potential to predict BOS and development of DSA following LT.