Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Neurosurgery, University of California San Francisco, San Francisco, California, USA.
J Neurotrauma. 2021 Apr 1;38(7):918-927. doi: 10.1089/neu.2020.7177. Epub 2020 Dec 28.
Systemic inflammation impacts outcome after traumatic brain injury (TBI), but most TBI biomarker studies have focused on brain-specific proteins. C-reactive protein (CRP) is a widely used biomarker of inflammation with potential as a prognostic biomarker after TBI. The ransforming esearch and linical nowledge in raumatic rain njury (TRACK-TBI) study prospectively enrolled TBI patients within 24 h of injury, as well as orthopedic injury and uninjured controls; biospecimens were collected at enrollment. A subset of hospitalized participants had blood collected on day 3, day 5, and 2 weeks. High-sensitivity CRP (hsCRP) and glial fibrillary acidic protein (GFAP) were measured. Receiver operating characteristic analysis was used to evaluate the prognostic ability of hsCRP for 6-month outcome, using the Glasgow Outcome Scale-Extended (GOSE). We included 1206 TBI subjects, 122 orthopedic trauma controls (OTCs), and 209 healthy controls (HCs). Longitudinal biomarker sampling was performed in 254 hospitalized TBI subjects and 19 OTCs. hsCRP rose between days 1 and 5 for TBI and OTC subjects, and fell by 2 weeks, but remained elevated compared with HCs ( < 0.001). Longitudinally, hsCRP was significantly higher in the first 2 weeks for subjects with death/severe disability (GOSE <5) compared with those with moderate disability/good recovery (GOSE ≥5); AUC was highest at 2 weeks (AUC = 0.892). Combining hsCRP and GFAP at 2 weeks produced AUC = 0.939 for prediction of disability. Serum hsCRP measured within 2 weeks of TBI is a prognostic biomarker for disability 6 months later. hsCRP may have utility as a biomarker of target engagement for anti-inflammatory therapies.
全身炎症反应对创伤性脑损伤（TBI）的预后有影响，但大多数 TBI 生物标志物研究都集中在脑特异性蛋白上。C 反应蛋白（CRP）是一种广泛使用的炎症标志物，具有作为 TBI 预后生物标志物的潜力。转化研究和临床现在知识在创伤性脑损伤（TRACK-TBI）研究前瞻性地招募了伤后 24 小时内的 TBI 患者，以及骨科损伤和未受伤的对照者；在入组时采集生物样本。一部分住院患者在第 3 天、第 5 天和第 2 周采集血液。测量高敏 C 反应蛋白（hsCRP）和胶质纤维酸性蛋白（GFAP）。使用格拉斯哥预后评分扩展版（GOSE）进行Receiver Operating Characteristic 分析，评估 hsCRP 对 6 个月结局的预后能力。我们纳入了 1206 名 TBI 患者、122 名骨科创伤对照者（OTCs）和 209 名健康对照者（HCs）。对 254 名住院 TBI 患者和 19 名 OTCs 进行了纵向生物标志物采样。TBI 和 OTC 患者的 hsCRP 在第 1 天至第 5 天之间升高，并在第 2 周下降，但仍高于 HCs（<0.001）。纵向来看，死亡/严重残疾（GOSE<5）的患者在伤后前 2 周 hsCRP 明显高于中度残疾/良好恢复（GOSE≥5）的患者（AUC 最高为 2 周时为 0.892）。将 hsCRP 和 GFAP 结合在 2 周内进行测量，可使残疾预测的 AUC 达到 0.939。TBI 后 2 周内测量的血清 hsCRP 是 6 个月后残疾的预后生物标志物。hsCRP 可能作为抗炎治疗的靶点效应标志物具有一定的应用价值。
