Evaluation of Acute Glial Fibrillary Acidic Protein and Ubiquitin C-Terminal Hydrolase-L1 Plasma Levels in Traumatic Brain Injury Patients with and without Intracranial Lesions

Abstract

This pilot study aimed to evaluate the association of plasma ubiquitin C-terminal hydrolase-L1 (UCH-L1), glial fibrillary acidic protein (GFAP), and S100 calcium-binding protein B (S100B) with intracranial abnormalities visible on a computed tomography (CT) scan (CT positive) and injury severity in acute traumatic brain injury (TBI). For these purposes, a cohort of 109 adult TBI patients was recruited within 6 h from the injury event. A hyperacute subcohort of 20 patients who had their blood collected within 2 h from injury was analyzed separately for early acute biomarker levels. Levels of GFAP and UCH-L1 were analyzed using the prototype Abbott i-STAT™ TBI Plasma Test (Abbott Laboratories, Abbot Park, IL), alongside S100B measurement (Elecsys; Roche Diagnostics, Penzberg, Germany). In the hyperacute subcohort, GFAP and UCH-L1, but not S100B, levels were significantly higher in the CT-positive group compared to CT-negative patients. AUC values for differentiation between CT-positive and CT-negative patients were 0.97 for GFAP, 0.87 for UCH-L1, and 0.60 for S100B. Severity discrimination, defined by Glasgow Coma Scale (GCS) score, was then analyzed in the total patient cohort. Levels of all three biomarkers were significantly different between mild (GCS, 13–15) and moderate/severe (GCS, 3–12) injury groups. UCH-L1 showed the highest area under the curve value for severity discrimination (0.94), followed by GFAP (0.91) and S100B (0.83). These results support the clinical utility of GFAP and UCH-L1 as TBI biomarkers able to rule out CT-positive injury in acute TBI. Moreover, excellent differentiation of GFAP and UCH-L1 between mild and moderate/severe TBI groups affirms their close association with the underlying pathology.

Challenges of the Effectiveness of Traumatic Brain Injuries Biomarkers in the Sports-Related Context

“…The area under the curve (AUC) was calculated from the ROC curves to assess the performance of early UCH-L1 levels in distinguishing TBI from control patients. Early UCH-L1 levels were able to distinguish TBI from uninjured control participants with an AUC 0.87 (95% CI 0.82–0.92), indicating good predictive accuracy [ 70 , 71 ]. The area under the curve for discriminating between positive and negative intracranial lesions on CT scan was 0.73 (95% CI 0.62–0.83) [ 70 ].…”

Blood Biomarkers in Neurodegenerative Diseases

“…An increase in its concentration in the blood has been found in patients after mild traumatic brain injury (TBI). 23,24 Recent studies have also shown that GFAP concentrations in the plasma are higher in patients with AD than in controls and are also associated with amyloid pathology. [25][26][27] High concentrations of plasma GFAP have also been reported in patients with frontotemporal lobar degeneration (FTLD)-related syndromes but to a lesser extent than those in patients with AD.…”

“…The intended use is for ruling out evidence of intracranial trauma on head CT. A pivotal multisite study of 1,176 individuals with acute mild TBI referenced in the US FDA documentation found this Abbott TBI diagnostic to have 99.3% negative predictive value for ruling out intracranial trauma. 23 Abbott is now developing its high throughput core laboratory ARCHITECT platform to run this assay and is also developing the i-STAT Alinity to function as a point-of-care test. GFAP can also be measured in the plasma using a commercially available Simoa-based assay.…”

Recent Advances in the Development of Biofluid-Based Prognostic Biomarkers of Diffuse Axonal Injury

“…The maximum serum concentration of S100B is reached 20 min after brain damage. The normal upper limit for this protein in relation to the detection of intracranial damage was defined as 0.1 μg/l based on a multicenter study in patients with mild TBI [122]. The measurement of S100B-protein can be influenced by patient age and gender in CSF samples but not in serum samples thus making it a practically feasible biomarker.…”