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PLoS One. 2014 Mar 25;9(3):e92698. doi: 10.1371/journal.pone.0092698. eCollection 2014.

Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products.

Author information

1
Banyan Biomarkers Inc., Alachua, Florida, United States of America.
2
Department of Psychiatry, Center for Neuroproteomics and Biomarker Research, University of Florida, Gainesville, Florida, United States of America.
3
University of Messina, Messina, Italy.
4
Department of Anesthesiology, University of Florida, Gainesville, Florida, United States of America.
5
Clinical and Health Psychology, University of Florida, Gainesville, Florida, United States of America.
6
Department of Neurosurgery, University of Pécs and Clinical Neuroscience Image Center of Hungarian Academy of Sciences (HAS) Pécs, Hungary.
7
Department of Psychology, University of Houston, Houston, Texas, United States of America.
8
Laboratory of Neurodegenerative Disease and CNS Biomarkers, Departments of Neurology and Physiology/Pharmacology, SUNY Downstate Medical Center, Brooklyn, New York, United States of America.
9
Center for Military Psychiatry and Neuroscience, Walter Reed Army Institute of Research, Silver Spring, Maryland, United States of America.
10
Department of Neurosurgery, Baylor College of Medicine, Houston, Texas, United States of America.

Erratum in

  • PLoS One. 2014;9(6):e101712.

Abstract

The role of systemic autoimmunity in human traumatic brain injury (TBI) and other forms of brain injuries is recognized but not well understood. In this study, a systematic investigation was performed to identify serum autoantibody responses to brain-specific proteins after TBI in humans. TBI autoantibodies showed predominant immunoreactivity against a cluster of bands from 38-50 kDa on human brain immunoblots, which were identified as GFAP and GFAP breakdown products. GFAP autoantibody levels increased by 7 days after injury, and were of the IgG subtype predominantly. Results from in vitro tests and rat TBI experiments also indicated that calpain was responsible for removing the amino and carboxyl termini of GFAP to yield a 38 kDa fragment. Additionally, TBI autoantibody staining co-localized with GFAP in injured rat brain and in primary rat astrocytes. These results suggest that GFAP breakdown products persist within degenerating astrocytes in the brain. Anti-GFAP autoantibody also can enter living astroglia cells in culture and its presence appears to compromise glial cell health. TBI patients showed an average 3.77 fold increase in anti-GFAP autoantibody levels from early (0-1 days) to late (7-10 days) times post injury. Changes in autoantibody levels were negatively correlated with outcome as measured by GOS-E score at 6 months, suggesting that TBI patients with greater anti-GFAP immune-responses had worse outcomes. Due to the long lasting nature of IgG, a test to detect anti-GFAP autoantibodies is likely to prolong the temporal window for assessment of brain damage in human patients.

PMID:
24667434
PMCID:
PMC3965455
DOI:
10.1371/journal.pone.0092698
[Indexed for MEDLINE]
Free PMC Article

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