title: Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein.
abstract: Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI]). Levels of the two biomarkers were weakly correlated to each other (r=0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and healthy controls (area under the curve [AUC] 0.87 and 0.91 for UCH-L1 and GFAP, respectively). When biomarkers were combined, superior sensitivity and specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers discriminated between TBI patients with intracranial lesions on CT scan and those without such lesions, but GFAP measures were significantly more sensitive and specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months after injury, neither biomarker had adequate sensitivity and specificity (AUC 0.65-0.74, for GFAP, and 0.59-0.80 for UCH-L1, depending upon Glasgow Outcome Scale Extended [GOS-E] threshold used). Our results support a role for multiple biomarker measurements in TBI research. ( ClinicalTrials.gov Identifier NCT01565551).
authors.affiliation: 1 Center for Neuroscience and Regenerative Medicine, Uniformed Services University of the Health Sciences , Bethesda, Maryland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
authors.forename: Linda
authors.initials: L
authors.lastname: Papa
authors.forename: Marco D
authors.initials: MD
authors.lastname: Sorani
authors.forename: John K
authors.initials: JK
authors.lastname: Yue
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McMahon
authors.forename: Tomoo
authors.initials: T
authors.lastname: Inoue
authors.forename: Esther L
authors.initials: EL
authors.lastname: Yuh
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.forename: Andrew I R
authors.initials: AI
authors.lastname: Maas
authors.forename: Alex B
authors.initials: AB
authors.lastname: Valadka
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging*; D001930:Brain Injuries / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging; D005260:Female; D015600:Glasgow Coma Scale; D005904:Glial Fibrillary Acidic Protein / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D011859:Radiography; D012680:Sensitivity and Specificity; D043222:Ubiquitin Thiolesterase / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D005904:Glial Fibrillary Acidic Protein; D043222:Ubiquitin Thiolesterase