Sex differences in time course and diagnostic accuracy of GFAP and UCH-L1 in trauma patients with mild traumatic brain injury

Abstract

Glial Fibrillary Acidic Protein (GFAP) and Ubiquitin C-terminal hydrolase (UCH-L1) have been FDA-approved for clinical use in mild and moderate traumatic brain injury (TBI). Understanding sex differences in their diagnostic accuracy over time will help inform clinical practice. We sought to evaluate the sex differences in the temporal profile of GFAP and UCH-L1 in a large cohort of trauma patients presenting to the emergency department. To compare the biomarkers’ diagnostic accuracy in male versus female patients for detecting mild TBI (MTBI), and traumatic intracranial lesions on head CT. This prospective cohort study enrolled female and male adult trauma patients presenting to a Level 1 Trauma Center. All patients underwent rigorous screening to determine whether or not they had experienced a MTBI. Of 3025 trauma patients assessed, 1030 met eligibility criteria and 446 declined. Initial blood samples were obtained in 584 patients enrolled within 4 h of injury. Repeated blood sampling was conducted at 4, 8, 12, 16, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, and 180-h post-injury. The main outcomes included the diagnostic accuracy in detection of MTBI and traumatic intracranial lesions on head CT scan. A total of 1831 samples were drawn in 584 patients over 7 days, 362 (62%) were male and 222 (38%) were female. The pattern of elevation was similar in both sexes. Although the pattern of elevation was similar between male and female for both biomarkers, male patients had significantly higher concentrations of UCH-L1 compared to female patients at several timepoints post-injury, particularly within 24 h of injury. There were no significant differences in diagnostic accuracy for detecting MTBI or for detecting CT lesions between male and female patients at any timepoint for both GFAP and UCH-L1. Although patterns of GFAP and UCH-L1 release in trauma patients over a week post-injury was similar between the sexes, there were significantly higher concentrations of UCH-L1 in males at several timepoints post-injury. Despite this, the overall diagnostic accuracies of both GFAP and UCH-L1 over time for detecting MTBI and CT lesions were not significantly different between male and female trauma patients.

The Importance of Increased Serum GFAP and UCH-L1 Levels in Distinguishing Large Vessel from Small Vessel Occlusion in Acute Ischemic Stroke

“…A recent study displayed higher concentrations of UCH-L1 in male patients compared to female, while similar findings were not found with GFAP. Regardless of these findings, the overall diagnostic precision did not significantly differ between sex groups [ 46 ]. Although there are differences in age and sex between our groups, their distribution reflects the general population and epidemiology of stroke, with older age and female sex linked to a worse burden of stroke mortality and disability [ 47 ].…”

mTBI Biological Biomarkers as Predictors of Postconcussion Syndrome—Review

“…GFAP is an intermediate filament protein that is highly specific for cells of astroglial lineage [56]. It is known as an astroglial marker of injury and is found in the astroglial skeleton of both white and gray brain matter [57]. It is also expressed by the Leydig cells of the testes [58].…”

Identifying the Target Traumatic Brain Injury Population for Hyperbaric Oxygen Therapy

“…Accumulating studies on TBI have shown sensitive biomarkers to determine the severity of the disease. Foremost are inflammatory biomarkers such as GFAP and UCH-L1 [84,85], which can be assayed in blood samples from TBI patients. For each sample draw, a single vial of approximately 2 mL of blood is collected and placed in serum separator tubes allowing it to clot at room temperature.…”