Department of Biochemistry and Molecular Biology, LSUHSC-School of Medicine, New Orleans, Louisiana.
J Neuropathol Exp Neurol. 2019 Mar 1;78(3):209-218. doi: 10.1093/jnen/nly129.
Veterans who have served in the military are at a nearly 60% greater risk of being diagnosed with amyotrophic lateral sclerosis (ALS). Literature reports suggest that a history of traumatic brain injury (TBI) may be a risk factor for ALS in veterans. However, no diagnostic biomarkers are available for identifying ALS risk/development in TBI-exposed veterans. Here, using a Wes assay, we show that ISGylation, a conjugated form of interferon-stimulated gene 15 protein, is significantly elevated in the lumbar spinal cords (SC-Ls) of TBI-ALS compared with ALS veterans without a previous history of TBI (nonTBI-ALS). Although not as striking as in TBI-ALS veterans, ISGylation is also increased in nonTBI-ALS compared with normal veterans. Notably, no changes in ISGylation were seen in occipital lobe samples obtained from the same patients, suggesting that elevated ISGylation is distinct to ALS disease-specific SC-Ls. Moreover, we detected increased ISGylation in cerebral spinal fluid samples of TBI-ALS veterans. Other results using cultured lymphocyte cell lines show a similar trend of increased ISGylation in ALS patients from the general population. Together, these data suggest that ISGylation could serve as a diagnostic biomarker for TBI-ALS veterans, nonTBI-ALS veterans, and nonveterans affected by ALS.
退伍军人患肌萎缩性侧索硬化症（ALS）的风险增加近 60%。文献报道表明，创伤性脑损伤（TBI）史可能是退伍军人患 ALS 的一个风险因素。然而，目前尚无诊断生物标志物可用于识别 TBI 暴露退伍军人的 ALS 风险/发展。在这里，我们使用 Wes 检测法显示，与没有创伤性脑损伤（非 TBI-ALS）病史的 ALS 退伍军人相比，ISGylation（干扰素刺激基因 15 蛋白的一种结合形式）在创伤性脑损伤-ALS（TBI-ALS）退伍军人的腰椎脊髓（SC-L）中显著升高。虽然与 TBI-ALS 退伍军人相比，ISGylation 的升高并不那么明显，但与正常退伍军人相比，非 TBI-ALS 退伍军人的 ISGylation 也升高了。值得注意的是，在从同一患者获得的枕叶样本中未观察到 ISGylation 的变化，这表明升高的 ISGylation 与 ALS 疾病特异性的 SC-L 不同。此外，我们在 TBI-ALS 退伍军人的脑脊液样本中检测到 ISGylation 的增加。使用培养的淋巴细胞细胞系进行的其他结果显示，一般人群中 ALS 患者的 ISGylation 也呈类似增加的趋势。这些数据表明，ISGylation 可以作为 TBI-ALS 退伍军人、非 TBI-ALS 退伍军人和受 ALS 影响的非退伍军人的诊断生物标志物。
