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

Zhiqun Zhang, J. Susie Zoltewicz, Stefania Mondello, Kimberly J. Newsom, Zhihui Yang, Boxuan Yang, Firas Kobeissy, Joy Guingab, Olena Glushakova, Steven Robicsek, Shelley Heaton, Andras Buki, Julia Hannay, Mark S. Gold, Richard Rubenstein, Xi Chun May Lu, Jitendra R. Dave, Kara Schmid, Frank Tortella, Claudia S. RobertsonKevin K.W. Wang

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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.

Original languageEnglish
Article numbere92698
JournalPloS one
Volume9
Issue number3
DOIs
Publication statusPublished - Mar 25 2014

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Zhang, Z., Zoltewicz, J. S., Mondello, S., Newsom, K. J., Yang, Z., Yang, B., Kobeissy, F., Guingab, J., Glushakova, O., Robicsek, S., Heaton, S., Buki, A., Hannay, J., Gold, M. S., Rubenstein, R., Lu, X. C. M., Dave, J. R., Schmid, K., Tortella, F., ... Wang, K. K. W. (2014). Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products. PloS one, 9(3), [e92698]. https://doi.org/10.1371/journal.pone.0092698