Non-invasive diagnosis of cardiac rejection using small non-coding RNAs

Abstract Background Endomyocardial biopsy is the standard technique for rejection surveillance in heart transplantation recipients and an invasive method with important limitations clearly associated both a risk of procedural complications serious long-term sequelae when performed repeatedly. All these considerations highlight need to identify non-invasive alternative methods capable discriminating between different grades reducing endomyocardial biopsy. Purpose We conducted non-targeted transcriptomic study focused on identifying serum small non-coding RNAs, mainly aimed less studied types, evaluate their diagnostic accuracy detecting episodes. Methods included consecutive samples from transplant undergoing routine biopsies. Non-coding RNA sequencing analysis (Illumina HiSeq 2500) was 40 samples, 28 diagnosed RCA (RCA Grade 1R, n=16; ≥2R, n=12) 12 without cardiac rejection. Results 636 RNAs were detected among scaRNAs, snoRNAs, snRNAs miscRNAs biotypes. But, neither piRNA nor siRNA biotypes detected. Of all them, 41 altered patients finding no alteration scaRNAs biotype. Three molecules miscRNA biotype showed best results excellent capacity moderate/severe rejection: RN7SL840P (AUC=0.938, p<0.01), Y_RNA [ENSG00000223302] (AUC=0.931, p<0.0001) [ENSG00000202273] (AUC=0.903, p<0.001). In addition, RN7SKP5 good diagnosis ≥2R (AUC=0.806, p<0.05) preserving at 1R (AUC=0.781, p<0.05). Conclusions The 6.5% have differential expression acute cellular non-detection piRNAs siRNAs stands out, as well absence propose levels potential biomarkers role due its RCA, since it also allows detection mild Funding Acknowledgement Type funding sources: Public grant(s) – National budget only. Main source(s): Institute Health Carlos III European Regional Development Fund (ERDF)