Point-of-Care Platform Blood Biomarker Testing of Glial Fibrillary Acidic Protein versus S100 Calcium-Binding Protein B for Prediction of Traumatic Brain Injuries: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study

Abstract

Glial fibrillary acidic protein (GFAP) is cleared by the Food and Drug Administration (FDA) to determine need for head computed tomography (CT) within 12 h after mild traumatic brain injury (TBI) (Glasgow Coma Score [GCS] 13-15); S100 calcium-binding protein B (S100B) serves this function in Europe. This phase 1 biomarker cohort analysis of the multi-center, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study compares GFAP's diagnostic performance, measured on a rapid point-of-care platform, against protein S100B to predict intracranial abnormalities on CT within 24 h post-injury across the spectrum of TBI (GCS 3-15). Head CT scan performed in TBI subjects and blood was collected for all consenting subjects presenting to 18 United States level 1 trauma centers. Plasma was analyzed on a point-of-care device prototype assay for GFAP and serum was analyzed for S100B. In 1359 patients with TBI (GCS 3-15), mean (standard deviation [SD]) age = 40.1 (17.0) years; 68% were male. Plasma GFAP levels were significantly higher in CT+ TBI subjects (median = 1358 pg/mL, interquartile range [IQR]: 472-3803) than in CT- TBI subjects (median = 116 pg/mL, IQR: 26-397) or orthopedic trauma controls (n = 122; median = 13 pg/mL, IQR: 7-20), p < 0.001. Serum S100B levels were likewise higher in CT+ TBI subjects (median = 0.17 μg/L, IQR: 0.09-0.38) than in CT- TBI subjects (median = 0.10 μg/L, IQR: 0.06-0.18), p < 0.001. Receiver operating characteristic curves were generated for prediction of intracranial injury on admission CT scan; area under the curve (AUC) for GFAP was significantly higher than for S100B in the same cohort (GFAP AUC - 0.85, 95% confidence interval [CI] 0.83-0.87; S100B AUC - 0.67, 95% CI 0.64-0.70; p < 0.001). GFAP, measured on a point-of-care platform prototype assay, has high discriminative ability to predict intracranial abnormalities on CT scan in patients with TBI across the full injury spectrum of GCS 3-15 through 24 h post-injury. GFAP substantially outperforms S100B.

Keywords: S100 calcium-binding protein B; biomarkers; glial fibrillary acidic protein; traumatic brain injury.

FIG. 1.

Consolidated Standards of Reporting Trials (CONSORT) diagram of subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study included in current analysis.

FIG. 2.

Plasma glial fibrillary acidic protein (GFAP) and serum S100 calcium-binding protein B (S100B) levels by head computed tomography (CT) result across full spectrum of traumatic brain injury (TBI) (Glasgow Coma Score [GCS] 3–15). Violin plots of GFAP (A) and S100B (B) levels in TBI subjects (all GCS 3–15) with negative and positive head CT scans for intracranial injuries. Patients negative for intracranial injury on CT (CT-, n = 810) had a mean plasma GFAP 363.8 pg/mL (standard deviation [SD] 706.3 pg/mL), whereas subjects positive for any intracranial lesion type (CT+, n = 549) had a mean plasma GFAP level 3970.1 pg/mL (SD 7819.6 pg/mL). Mean S100B levels were 0.181 ug/L (SD 0.778 ug/L) in the negative CT group (n = 753) and 0.405 ug/L (SD 1.236 ug/L) in the positive head CT group (n = 534). (C) Box plots of GFAP levels in plasma indicating higher levels of GFAP with progressively more severe intracranial injury spectra on head CT. Red dots indicate mean values. SAH, subarachnoid hemorrhage; SDH, subdural hematoma. Color image is available online.

FIG. 3.

Receiver operating-characteristic curve comparing performance of plasma glial fibrillary acidic protein (GFAP) and serum S100 calcium-binding protein B (S100B) as biomarkers for predicting intracranial injury on head CT scan within 24 h of injury across the full spectrum of traumatic brain injury (TBI) (Glasgow Coma Score [GCS] 3–15). The area under the curve (AUC) demonstrates that GFAP significantly outperforms S100B. GFAP measurements were performed on a point-of-care platform prototype assay capable of returning results within 15 min. Color image is available online.