1 Department of Neurosurgery, Turku University Hospital, Turku, Finland.
2 Turku Brain Injury Center, Turku University Hospital, Turku, Finland.
J Neurotrauma. 2019 Jul 15;36(14):2178-2189. doi: 10.1089/neu.2018.6254. Epub 2019 Apr 5.
The aim of the study was to examine the ability of eight protein biomarkers and their combinations in discriminating computed tomography (CT)-negative and CT-positive patients with traumatic brain injury (TBI), utilizing highly sensitive immunoassays in a well-characterized cohort. Blood samples were obtained from 160 patients with acute TBI within 24 h of admission. Levels of β-amyloid isoforms 1-40 (Aβ40) and 1-42 (Aβ42), glial fibrillary acidic protein (GFAP), heart fatty-acid binding protein (H-FABP), interleukin 10 (IL-10), neurofilament light (NF-L), S100 calcium-binding protein B (S100B), and tau were measured. Patients were divided into CT-negative ( = 65) and CT-positive ( = 95), and analyses were conducted separately for TBIs of all severities (Glasgow Coma Scale [GCS] score 3-15) and mild TBIs (mTBIs; GCS 13-15). NF-L, GFAP, and tau were the best in discriminating CT-negative and CT-positive patients, both in patients with mTBI and with all severities. In patients with all severities, area under the curve of the receiver operating characteristic (AUC) was 0.822, 0.817, and 0.781 for GFAP, NF-L, and tau, respectively. In patients with mTBI, AUC was 0.720, 0.689, and 0.676, for GFAP, tau, and NF-L, respectively. The best panel of three biomarkers for discriminating CT-negative and CT-positive patients in the group of all severities was a combination of GFAP+H-FABP+IL-10, with a sensitivity of 100% and specificity of 38.5%. In patients with mTBI, the best panel of three biomarkers was H-FABP+S100B+tau, with a sensitivity of 100% and specificity of 46.4%. Panels of biomarkers outperform individual biomarkers in separating CT-negative and CT-positive patients. Panels consisted mainly of different biomarkers than those that performed best as an individual biomarker.
本研究旨在利用高灵敏度免疫分析法，在特征明确的队列中，检验 8 种蛋白生物标志物及其组合在区分 CT 阴性和 CT 阳性创伤性脑损伤 (TBI) 患者方面的能力。研究纳入了 160 例发病 24 小时内的急性 TBI 患者的血液样本。检测了β淀粉样蛋白 1-40 (Aβ40) 和 1-42 (Aβ42)、神经胶质纤维酸性蛋白 (GFAP)、心脏脂肪酸结合蛋白 (H-FABP)、白细胞介素 10 (IL-10)、神经丝轻链 (NF-L)、S100 钙结合蛋白 B (S100B) 和 tau 的水平。患者被分为 CT 阴性（ = 65）和 CT 阳性（ = 95），并分别对所有严重程度（格拉斯哥昏迷量表 [GCS] 评分 3-15）和轻度 TBI（mTBI；GCS 13-15）的 TBI 患者进行分析。NF-L、GFAP 和 tau 是区分 CT 阴性和 CT 阳性患者的最佳标志物，无论是在 mTBI 患者还是所有严重程度的患者中都是如此。在所有严重程度的患者中，GFAP、NF-L 和 tau 的受试者工作特征曲线下面积（AUC）分别为 0.822、0.817 和 0.781。在 mTBI 患者中，AUC 分别为 0.720、0.689 和 0.676。在所有严重程度患者中，用于区分 CT 阴性和 CT 阳性患者的最佳 3 种生物标志物组合是 GFAP+H-FABP+IL-10，其敏感性为 100%，特异性为 38.5%。在 mTBI 患者中，最佳的 3 种生物标志物组合是 H-FABP+S100B+tau，其敏感性为 100%，特异性为 46.4%。生物标志物组合在区分 CT 阴性和 CT 阳性患者方面优于单个标志物。组合主要由与作为单个标志物表现最佳的标志物不同的标志物组成。
