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Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury*

Papa, Linda MDCM, MSc; Akinyi, Linnet MS; Liu, Ming Cheng PhD; Pineda, Jose A. MD; Tepas, Joseph J. III MD; Oli, Monika W. PhD; Zheng, Wenrong PhD; Robinson, Gillian PhD; Robicsek, Steven A. MD; Gabrielli, Andrea MD; Heaton, Shelley C. PhD; Hannay, H Julia PhD; Demery, Jason A. PhD; Brophy, Gretchen M. PharmD; Layon, Joe MD; Robertson, Claudia S. MD; Hayes, Ronald L. PhD; Wang, Kevin K. W. PhD

doi: 10.1097/CCM.0b013e3181b788ab
Clinical Investigations

Objective: Ubiquitin C-terminal hydrolase (UCH-L1), also called neuronal-specific protein gene product (PGP 9.3), is highly abundant in neurons. To assess the reliability of UCH-L1 as a potential biomarker for traumatic brain injury (TBI) this study compared cerebrospinal fluid (CSF) levels of UCH-L1 from adult patients with severe TBI to uninjured controls; and examined the relationship between levels with severity of injury, complications and functional outcome.

Design: This study was designed as prospective case control study.

Patients: This study enrolled 66 patients, 41 with severe TBI, defined by a Glasgow coma scale (GCS) score of ≤8, who underwent intraventricular intracranial pressure monitoring and 25 controls without TBI requiring CSF drainage for other medical reasons.

Setting: Two hospital system level I trauma centers.

Measurements and Main Results: Ventricular CSF was sampled from each patient at 6, 12, 24, 48, 72, 96, 120, 144, and 168 hrs following TBI and analyzed for UCH-L1. Injury severity was assessed by the GCS score, Marshall Classification on computed tomography and a complicated postinjury course. Mortality was assessed at 6 wks and long-term outcome was assessed using the Glasgow outcome score 6 months after injury. TBI patients had significantly elevated CSF levels of UCH-L1 at each time point after injury compared to uninjured controls. Overall mean levels of UCH-L1 in TBI patients was 44.2 ng/mL (±7.9) compared with 2.7 ng/mL (±0.7) in controls (p <.001). There were significantly higher levels of UCH-L1 in patients with a lower GCS score at 24 hrs, in those with postinjury complications, in those with 6-wk mortality, and in those with a poor 6-month dichotomized Glasgow outcome score.

Conclusions: These data suggest that this novel biomarker has the potential to determine injury severity in TBI patients. Further studies are needed to validate these findings in a larger sample.

Department of Emergency Medicine (LP), Orlando Regional Medical Center, Orlando, FL; Banyan Biomarkers Inc. (LA, MCL, MWO, GR), Alachua, FL; Departments of Pediatrics and Neurology (JAP), Washington University, St. Louis, MO; Departments of Surgery and Pediatrics (JJT), University of Florida, Jacksonville, FL; Center for Traumatic Brain Injury Studies (WZ), University of Florida, Gainesville, FL; Department of Anesthesia (SAR, AG, JL), University of Florida, Gainesville, FL; Department of Clinical and Health Psychology (SCH), University of Florida, Gainesville, FL; Department of Psychology (HJH), University of Houston, Houston, TX; Department of Psychology (JAD), VA Hospital, Gainesville, FL; Departments of Pharmacy and Neurosurgery (GMB), Virginia Commonwealth University, Richmond, VA; Department of Neurosurgery (CSR), Baylor College of Medicine, Houston, TX; and Center of Innovative Research (RLH, KKWW), Banyan Biomarkers Inc., Alachua, FL.

Drs. Papa, Hayes, and Wang are consultants for Banyan Biomarkers. The remaining authors have not disclosed any potential conflicts of interest.

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© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins