26 - Saliva microRNA signatures in children with moderate-to-severe brain injury

Poster Number: 26
Publication Number: 26.201

Robert R. Ciancaglini, Penn State Children's Hospital, Hershey, PA, United States; Steven Hicks, Pennsylvania State University College of Medicine, Hershey, PA, United States; Neal J. Thomas, Pennsylvania State University College of Medicine, Hershey, PA, United States; Kent P. Hymel, Pennsylvania State University College of Medicine, Hershey, PA, United States; Veronica Armijo-Garcia, UT Health San Antonio, San Antonio, TX, United States; Ann S. Botash, Ann Botash/SUNY Upstate, Syracuse, NY, United States; Mark Gallo, Penn State College of Medicine, Lemoyne, PA, United States

Background: Traumatic brain injury (TBI) is the leading cause of death and long term disability for children in the United States. Despite this burden, physicians lack objective tools to aide in prognostication of outcomes following severe TBI. Such a tool could help guide family counselling and medical decision making. We previously established a panel of salivary micro-ribonucleic acid (miRNA) specific to children who suffered a mild TBI, and predicted symptom severity and duration. However, no studies have examined whether this innovation can be applied to moderate-to-severe TBI.

Objective: The objective of this study was to identify a panel of salivary miRNAs that are specific to children with moderate-to-severe TBI, and examine whether TBI-related miRNAs change during the acute phase of recovery.

Design/Methods: In this multi-center, prospective, longitudinal case-control study we collected saliva from 12 children (1-14 years) with moderate-to-severe-TBI over 2 time-points: at admission (T1), and 24-36 hours after injury (T2). Saliva was also collected from age- and sex-matched controls admitted for other traumatic injuries, excluding those with trauma of the head or neck. Saliva miRNA levels were quantified with HiSeq technology. Mann-Whitney test was used to compare normalized, scaled miRNA levels between control and TBI groups (at T1). Wilcoxon Rank test was used to assess within-subjects changes in miRNA levels across T1 and T2. False detection rate (FDR) correction was applied to all results.

Results: Four miRNAs differed between control and TBI groups (FDR < 0.05). Three miRNAs were downregulated in children with TBI (miR-432-5p, miR-99b-5p, and miR-219a-5p). One miRNA was upregulated in children with TBI (miR-451b). Within children with TBI, there were two miRNAs with nominal changes (raw p < 0.05, FDR > 0.05) between T1 and T2: miR-202-5p was upregulated at T2 (fold change: 0.036; FDR = 0.29), and miR-149-3p was downregulated at T2 (fold change: 45.99 FDR = 0.26).Conclusion(s): Saliva miRNA levels are perturbed in children with moderate-to-severe TBI, and display longitudinal change in the acute post-injury period. These represent different miRNAs than are found to be perturbed in mild TBI. Further studies are necessary to confirm these findings in a larger cohort and determine whether miRNA levels can predict functional outcomes.