TY  - JOUR
PY  - 2014//
TI  - Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products
JO  - PLoS one
A1  - Zhang, Zhiqun
A1  - Zoltewicz, J. Susie
A1  - Mondello, Stefania
A1  - Newsom, Kimberly J.
A1  - Yang, Zhihui
A1  - Yang, Boxuan
A1  - Kobeissy, Firas
A1  - Guingab, Joy
A1  - Glushakova, Olena
A1  - Robicsek, Steven
A1  - Heaton, Shelley
A1  - Büki, Andras
A1  - Hannay, Julia
A1  - Gold, Mark S.
A1  - Rubenstein, Richard
A1  - Lu, Xi-Chun May
A1  - Dave, Jitendra R.
A1  - Schmid, Kara
A1  - Tortella, Frank
A1  - Robertson, Claudia S.
A1  - Wang, Kevin K. W.
SP  - e92698
EP  - e92698
VL  - 9
IS  - 3
N2  - 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. <br><br>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.<p />  <p>Language: en</p>
LA  - en
SN  - 1932-6203
UR  - http://dx.doi.org/10.1371/journal.pone.0092698
ID  - ref1
ER  -