TY - JOUR AU - Hogg, Marion C. AU - Raoof, Rana AU - El Naggar, Hany AU - Monsefi, Naser AU - Delanty, Norman AU - O’Brien, Donncha F. AU - Bauer, Sebastian AU - Rosenow, Felix AU - Henshall, David C. AU - Prehn, Jochen H.M. T1 - Elevation of plasma tRNA fragments precedes seizures in human epilepsy PY - 2019/07/01/ AB - Transfer RNAs (tRNAs) are a major class of noncoding RNA. Stress-induced cleavage of tRNA is highly conserved and results in tRNA fragments. Here, we found that specific tRNA fragments in plasma are associated with epilepsy. Small RNA-Seq of plasma samples collected during video EEG monitoring of patients with focal epilepsy identified significant differences in 3 tRNA fragments (5′GlyGCC, 5′AlaTGC, and 5′GluCTC) compared with samples from healthy controls. The levels of these tRNA fragments were higher in pre-seizure than in post-seizure samples, suggesting that they may serve as biomarkers of seizure risk in patients with epilepsy. In vitro studies confirmed that production and extracellular release of tRNA fragments were lower after epileptiform-like activity in hippocampal neurons. We designed PCR-based assays to quantify tRNA fragments in a cohort of pre- and post-seizure plasma samples from patients with focal epilepsy and from healthy controls. Receiver operating characteristic analysis indicated that tRNA fragments potently distinguished pre- from post-seizure patients. Elevated levels of tRNA fragments were not detected in patients with psychogenic nonepileptic seizures and did not result from medication tapering. This study potentially identifies a new class of epilepsy biomarker and reveals the possible existence of prodromal molecular patterns in blood that could be used to predict seizure risk. JF - The Journal of Clinical Investigation JA - J Clin Invest SN - 0021-9738 DO - 10.1172/JCI126346 VL - 129 IS - 7 UR - https://doi.org/10.1172/JCI126346 SP - 2946 EP - 2951 PB - The American Society for Clinical Investigation ER -