Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products.
Human traumatic brain injury induces autoantibody response against glial fibrillary acidic protein and its breakdown products.
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人类创伤性脑损伤诱导针对神经胶质纤维酸性蛋白及其分解产物的自身抗体反应。
DOI：
10.1371/journal.pone.0092698
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang KK
中科院分区：
文献类型：
--
作者：
Zhang Z;Zoltewicz JS;Mondello S;Newsom KJ;Yang Z;Yang B;Kobeissy F;Guingab J;Glushakova O;Robicsek S;Heaton S;Buki A;Hannay J;Gold MS;Rubenstein R;Lu XC;Dave JR;Schmid K;Tortella F;Robertson CS;Wang KK
系统性自身免疫在人类创伤性脑损伤 (TBI) 和其他形式的脑损伤中的作用已得到认可，但尚不清楚。在这项研究中，进行了一项系统研究，以确定人类 TBI 后血清自身抗体对大脑特异性蛋白质的反应。 TBI 自身抗体对人脑免疫印迹上 38-50 kDa 的一系列条带表现出主要的免疫反应性，这些条带被鉴定为 GFAP 和 GFAP 分解产物。损伤后7天GFAP自身抗体水平升高，且以IgG亚型为主。体外测试和大鼠 TBI 实验的结果还表明，钙蛋白酶负责去除 GFAP 的氨基和羧基末端，产生 38 kDa 的片段。此外，TBI 自身抗体染色与受损大鼠大脑和原代大鼠星形胶质细胞中的 GFAP 共定位。这些结果表明 GFAP 分解产物持续存在于大脑中退化的星形胶质细胞中。抗 GFAP 自身抗体也可以进入培养物中的活星形胶质细胞，其存在似乎会损害神经胶质细胞的健康。 TBI 患者的抗 GFAP 自身抗体水平从受伤后早期（0-1 天）到晚期（7-10 天）平均增加了 3.77 倍。自身抗体水平的变化与 6 个月时 GOS-E 评分测量的结果呈负相关，这表明抗 GFAP 免疫反应较强的 TBI 患者的结果较差。由于 IgG 的持久性，检测抗 GFAP 自身抗体的测试可能会延长评估人类患者脑损伤的时间窗口。
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.
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