Plasma Anti-Glial Fibrillary Acidic Protein Autoantibody Levels during the Acute and Chronic Phases of Traumatic Brain Injury: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot Study

• Published in: Journal of neurotrauma Vol. 33; no. 13; pp. 1270 - 1277
• Main Authors: Wang, Kevin K W, Yang, Zhihui, Yue, John K, Zhang, Zhiqun, Winkler, Ethan A, Puccio, Ava M, Diaz-Arrastia, Ramon, Lingsma, Hester F, Yuh, Esther L, Mukherjee, Pratik, Valadka, Alex B, Gordon, Wayne A, Okonkwo, David O, Manley, Geoffrey T, Cooper, Shelly R, Dams-O'Connor, Kristen, Hricik, Allison J, Inoue, Tomoo, Maas, Andrew I R, Menon, David K, Schnyer, David M, Sinha, Tuhin K, Vassar, Mary J
• Format: Journal Article
• Language: English
• Published: United States Mary Ann Liebert, Inc 01.07.2016
• Subjects: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies - blood; Brain Injuries, Traumatic - blood; Brain Injuries, Traumatic - physiopathology; Chronic Disease; Female; Glial Fibrillary Acidic Protein - immunology; Humans; Male; Middle Aged; Pilot Projects; Plasma; Proteins; Short Communication; Studies; Traumatic brain injury; Young Adult; traumatic brain injury; autoantibody; autoimmunity; glia; biomarkers
• ISSN: 0897-7151; 1557-9042
• DOI: 10.1089/neu.2015.3881

We described recently a subacute serum autoantibody response toward glial fibrillary acidic protein (GFAP) and its breakdown products 5-10 days after severe traumatic brain injury (TBI). Here, we expanded our anti-GFAP autoantibody (AutoAb[GFAP]) investigation to the multicenter observational study Transforming Research and Clinical Knowledge in TBI Pilot (TRACK-TBI Pilot) to cover the full spectrum of TBI (Glasgow Coma Scale 3-15) by using acute (<24 h) plasma samples from 196 patients with acute TBI admitted to three Level I trauma centers, and a second cohort of 21 participants with chronic TBI admitted to inpatient TBI rehabilitation. We find that acute patients self-reporting previous TBI with loss of consciousness (LOC) (n = 43) had higher day 1 AutoAb[GFAP] (mean ± standard error: 9.11 ± 1.42; n = 43) than healthy controls (2.90 ± 0.92; n = 16; p = 0.032) and acute patients reporting no previous TBI (2.97 ± 0.37; n = 106; p < 0.001), but not acute patients reporting previous TBI without LOC (8.01 ± 1.80; n = 47; p = 0.906). These data suggest that while exposure to TBI may trigger the AutoAb[GFAP] response, circulating antibodies are elevated specifically in acute TBI patients with a history of TBI. AutoAb[GFAP] levels for participants with chronic TBI (average post-TBI time 176 days or 6.21 months) were also significantly higher (15.08 ± 2.82; n = 21) than healthy controls (p < 0.001). These data suggest a persistent upregulation of the autoimmune response to specific brain antigen(s) in the subacute to chronic phase after TBI, as well as after repeated TBI insults. Hence, AutoAb[GFAP] may be a sensitive assay to study the dynamic interactions between post-injury brain and patient-specific autoimmune responses across acute and chronic settings after TBI.