National Neurotrauma Society
dateJuly 11-14, 2021
The National Neurotrauma Society is committed to the promotion of neurotrauma research by enhancing communications, providing a forum, and increasing support on the national and international level. The National Neurotrauma Society seeks to accelerate research that will provide answers for clinicians and ultimately improve the treatments available to patients. The National Neurotrauma Society will continue to promote excellence in the field by providing opportunities for scientists, establishing standards in both basic and clinical research, encouraging and supporting research, and promoting liaisons with other organizations that influence the care and cure of neurotrauma victims.
Quanterix will be participating in the conference with a virtual exhibit. Chat with our Simoa® experts to learn about the advances that ultra-sensitive Simoa technology continues to make in the study of neurology by enabling researchers to quantify biomarkers of TBI and other neurological injuries at fg/mL levels in blood.
S09 – Emerging Trends in Molecular TBI Biomarkers
4:00-5:15pm ET, Monday, July 12
Posters featuring Simoa technology:
LONGITUDINAL CHARACTERIZATION OF SERUM GLIAL FIBRILLARY ACIDIC PROTEIN AND ANTI-GFAP AUTOANTIBODIES AFTER TBI
Joshua Wiener1, Leah Vaughn1, Kevin Wang2, Amy Wagner1
1 University of Pittsburgh, Department of Physical Medicine and
Rehabilitation, Pittsburgh, USA
2 University of Florida, Department of Emergency Medicine,
Traumatic brain injury (TBI) triggers an autoimmune response to glial fibrillary acid protein (GFAP), a filament protein expressed by astrocytes in the CNS, which may manifest in serum as well through elevated GFAP and anti-GFAP autoantibodies (AGA) immunoglobulin (Ig)M and IgG. We aimed to characterize this response by collection of serial serum samples through month-six post-injury from n=361 individuals with moderate-to-severe-TBI. GFAP was measured via Quanterix SIMOA and AGA IgM and IgG by a customized ELISA. Biomarker data was aggregated into Day-0-6 and Month-1-6 means for analysis. Demographic and clinical factors were assessed and outcome measures using Disability Rating Scale (DRS) and Glasgow Outcome Scale (GOS) scores at 6- and 12-months post-TBI. Longitudinal biomarker patterns were characterized Day-0-6 and Month-1-6 by group-based trajectory (TRAJ) analysis. GFAP TRAJs showed decreasing trends over Day-0-6 and Month-1-6 while AGA IgM and IgG TRAJ profiles were zero-order over both time periods. Longitudinal (Day-0-6 vs. Month-1-6) correlations were evident for each biomarker. Day-0-6 GFAP TRAJs were linked to AGA expression over time, wherein the high GFAP TRAJ had higher AGA IgG and lower IgM:IgG in both time epochs. Older age was associated with higher Day-0-6 GFAP and AGA IgG and lower Day-0-6 and Month-1-6 AGA IgM and AGA IgM:IgG. Higher AGA IgG and lower AGA IgM:IgG at Day-0-6 were associated with worse DRS at 6- and 12-months post-injury. Month-1-6 AGA associations to outcome were not evident. Higher GFAP levels, however, at both Day-0-6 and Month-1-6, were associated with worse DRS and GOS score. These findings further motivate the characterization and mechanistic exploration of serum GFAP and AGA relationships to global recovery post-TBI.
EXTRACELLULAR VESICLE LEVELS OF CNS DAMAGE-ASSOCIATED PROTEINS IN TRAUMA WITH AND WITHOUT TRAUMATIC BRAIN INJURY
Vivian Guedes2, Sara Mithani2, Ethan Smith2, Dilorom Sass2, Cyndi Williams1, Jessica Gill2, Holly Hinson1
1 Oregon Health and Science University, Neurology, Portland,
2 National Institute of Nursing Research, Division of Intramural
Research, Bethesda, USA
Introduction: Extracellular vesicles (EVs) are membrane-bound vesicles that play a role in intracellular communication. EVs are an emerging biomarker after traumatic brain injury (TBI), as their lipid bilayer confers relative stability.
Methods: A subset of subjects from a prospective, observational trial with major trauma admitted to ICU were analyzed. Here, we included subjects with Multiple Injuries and Isolated Body Injury based on the Abbreviated Injury Severity Scores (AIS). Admission plasma samples were obtained within 6-12 hours of trauma. Total EV levels of glial (glial fibrillary acidic protein (GFAP)) and neuronal/axonal (ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), neurofilament light chain (NFL), and total-tau (t-tau)) proteins were measured using single molecule array (Simoa) technology and reported in pg/mL. Continuous variables were compared with t-tests; categorical variables with chi-squared tests. Correlations were measured with a Spearman’s correlation coefficient. Significance was set at P < 0.05.
Results: Patients with multiple injuries (n=41) and isolated body injury (n=73) were of similar age (47 +/- 17 v. 47 +/- 17 years, P=0.98) and predominately male (71% v. 74%, P=0.88). Patients with multiple injuries were as expected, more severely injured with higher injury severity scores (29 [26-41] v. 21 [14-26], P < 0.001), and lower GCS scores (12[4-13] v. 13[13-13], P < 0.001). Total body concentration EVs of GFAP, UCH-L1, and NFL were higher in those with multiple injuries (1768 [932-4780] v. 239 [63-589], P < 0.001), (75.4 [47.8-158.3] v. 41.5 [21.5-67.1], P=0.03), and (7.5 [3.3-12.3] v. 2.9 [2.1-4.8], P < 0.001), respectively. There was a weak, but significant correlation between total injury severity score and 3 of the proteins (GFAP ρ=0.46, P < 0.001; UCHL-1 ρ=0.38, P < 0.001; NFL ρ=0.36, P < 0.001).
Conclusion: While significantly higher in patients with TBI, EVs containing CNS damage associated proteins are present in trauma patients without clinically significant TBI. GFAP, UCH-L1, and NFL EVs weakly correlate to total injury severity.
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