Prediction of Functional Outcome in Patients with Acute Stroke by Measuring tRNA Derivatives

Abstract

<b><i>Background and Purpose:</i></b> Transfer RNA (tRNA) is a noncoding RNA that delivers amino acids to ribosomes for protein synthesis. tRNA is also involved in cell stress response programs. Oxidative stress induces direct conformational change in tRNA structure that promotes subsequent tRNA fragmentation. Using an antibody against tRNA-specific modified nucleoside 1-methyladenosine (m1A), we can detect tRNA derivatives such as conformationally changed tRNA, tRNA-derived fragments, and mononucleotide-free m1A. Based on these findings, tRNA derivatives may have potential as an early tissue damage marker. The purpose of this study was to investigate the plasma tRNA derivatives in stroke patients to clarify whether tRNA derivatives in the acute phase can detect early brain damage and then predict the functional outcome. <b><i>Methods:</i></b> Patients (75 patients with ischemic and 66 with hemorrhagic stroke) and 22 healthy volunteers were prospectively enrolled for this study between November 2016 and February 2019. Plasma samples were collected within 24 h and at 1 day, 7 days, and 30 days from the onset. Plasma tRNA derivative concentrations were measured by ELISA kit using the anti-m1A antibody. <b><i>Results:</i></b> The plasma tRNA derivative level on admission was significantly increased in both ischemic (mean ± standard error, 232.2 ± 33.1 ng/mL) and hemorrhagic stroke patients (212 ± 23.4 ng/mL) compared to the healthy volunteers (86.0 ± 7.9 ng/mL) (<i>p</i> = 0.00042 and <i>p</i> = 0.00018, respectively). The infarction size (<i>r</i> = 0.445, <i>p</i> = 0.00018) and hematoma volumes (<i>r</i> = 0.33, <i>p</i> = 0.0072) were also significantly correlated with tRNA derivatives. The concentrations of tRNA derivatives were associated with poor functional outcome (Modified Rankin Scale score 3–6 at 30 days from the onset) in patients with ischemic stroke at 7 days after onset (<i>p</i> = 0.020). <b><i>Conclusions:</i></b> Stress-induced tRNA derivatives can detect brain tissue damage, predicting functional outcome in patients with ischemic stroke.