title: 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.
abstract: 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.
authors.affiliation: 1 Departments of Psychiatry and Neuroscience, University of Florida , Gainesville, Florida.
authors.forename: Kevin K W
authors.initials: KK
authors.lastname: Wang
authors.affiliation: 1 Departments of Psychiatry and Neuroscience, University of Florida , Gainesville, Florida.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yang
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco General Hospital , San Francisco, California.|3 Department of Neurological Surgery, University of California , San Francisco, San Francisco, California.
authors.forename: John K
authors.initials: JK
authors.lastname: Yue
authors.affiliation: 1 Departments of Psychiatry and Neuroscience, University of Florida , Gainesville, Florida.
authors.forename: Zhiqun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco General Hospital , San Francisco, California.|3 Department of Neurological Surgery, University of California , San Francisco, San Francisco, California.
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Winkler
authors.affiliation: 4 Department of Neurological Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.affiliation: 5 Department of Neurology, Uniformed Services University of the Health Sciences , and Center for Neuroscience and Regenerative Medicine, Bethesda, Maryland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Diaz-Arrastia
authors.affiliation: 6 Department of Public Health, Erasmus Medical Center , Rotterdam, The Netherlands .
authors.forename: Hester F
authors.initials: HF
authors.lastname: Lingsma
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco General Hospital , San Francisco, California.|7 Department of Radiology, University of California , San Francisco, San Francisco, California.
authors.forename: Esther L
authors.initials: EL
authors.lastname: Yuh
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco General Hospital , San Francisco, California.|7 Department of Radiology, University of California , San Francisco, San Francisco, California.
authors.forename: Pratik
authors.initials: P
authors.lastname: Mukherjee
authors.affiliation: 8 Seton Brain and Spine Institute , Austin, Texas.
authors.forename: Alex B
authors.initials: AB
authors.lastname: Valadka
authors.affiliation: 9 Department of Rehabilitation Medicine, Mount Sinai School of Medicine , New York, New York.
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Gordon
authors.affiliation: 4 Department of Neurological Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco General Hospital , San Francisco, California.|3 Department of Neurological Surgery, University of California , San Francisco, San Francisco, California.
authors.forename: Geoffrey T
authors.initials: GT
authors.lastname: Manley
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco General Hospital , San Francisco, California.|3 Department of Neurological Surgery, University of California , San Francisco, San Francisco, California.|6 Department of Public Health, Erasmus Medical Center , Rotterdam, The Netherlands .
authors.forename: Shelly R
authors.initials: SR
authors.lastname: Cooper
authors.affiliation: 9 Department of Rehabilitation Medicine, Mount Sinai School of Medicine , New York, New York.
authors.forename: Kristen
authors.initials: K
authors.lastname: Dams-O'Connor
authors.affiliation: 4 Department of Neurological Surgery, University of Pittsburgh Medical Center , Pittsburgh, Pennsylvania.
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Hricik
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco General Hospital , San Francisco, California.|3 Department of Neurological Surgery, University of California , San Francisco, San Francisco, California.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Inoue
authors.affiliation: 10 Department of Neurosurgery, Antwerp University Hospital , Edegem, Belgium .
authors.forename: Andrew I R
authors.initials: AI
authors.lastname: Maas
authors.affiliation: 11 Division of Anaesthesia, University of Cambridge and Addenbrooke's Hospital , Cambridge, United Kingdom .
authors.forename: David K
authors.initials: DK
authors.lastname: Menon
authors.affiliation: 12 Department of Psychology, University of Texas , Austin, Texas.
authors.forename: David M
authors.initials: DM
authors.lastname: Schnyer
authors.affiliation: 7 Department of Radiology, University of California , San Francisco, San Francisco, California.
authors.forename: Tuhin K
authors.initials: TK
authors.lastname: Sinha
authors.affiliation: 2 Brain and Spinal Injury Center, San Francisco General Hospital , San Francisco, California.|3 Department of Neurological Surgery, University of California , San Francisco, San Francisco, California.
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Vassar
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D000070642:Brain Injuries, Traumatic / Q000097:blood* / Q000503:physiopathology*; D002908:Chronic Disease; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D005904:Glial Fibrillary Acidic Protein
keywords: autoantibody; autoimmunity; biomarkers; glia; traumatic brain injury