Newell Elizabeth, Shellington David K, Simon Dennis W, Bell Michael J, Kochanek Patrick M, Feldman Keri, Bayir Hülya, Aneja Rajesh K, Carcillo Joseph A, Clark Robert S B
1Department of Pediatrics, University of Iowa, Iowa City, IA. 2Department of Pediatrics, University of California San Diego, La Jolla, CA. 3Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA. 4Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA. 5The Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA. 6Safar Center for Resuscitation Research, University of Pittsburgh School of Medicine, Pittsburgh, PA. 7Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA. 8Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA. 9Department of Environmental and Occupational Health, University of Pittsburgh School of Medicine, Pittsburgh, PA. 10Clinical and Translational Science Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA.
Pediatr Crit Care Med. 2015 Jul;16(6):549-57. doi: 10.1097/PCC.0000000000000400.
The magnitude and role of the cellular immune response following pediatric traumatic brain injury remains unknown. We tested the hypothesis that macrophage/microglia and T-cell activation occurs following pediatric traumatic brain injury by measuring cerebrospinal fluid levels of soluble cluster of differentiation 163 and ferritin and soluble interleukin-2 receptor α, respectively, and determined whether these biomarkers were associated with relevant clinical variables and outcome.
Retrospective analysis of samples from an established, single-center cerebrospinal fluid bank.
PICU in a tertiary children's hospital.
Sixty-six pediatric patients after severe traumatic brain injury (Glasgow Coma Scale score < 8) who were 1 month to 16 years old and 17 control patients who were 1 month to 14 years old.
None.
Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor α were determined by enzyme-linked immunosorbent assay at two time points (t1 = 17 ± 10 hr; t2 = 72 ± 15 hr) for each traumatic brain injury patient. Cerebrospinal fluid levels of soluble cluster of differentiation 163, ferritin, and soluble interleukin-2 receptor α after traumatic brain injury were compared with controls and analyzed for associations with age, patient sex, initial Glasgow Coma Scale score, diagnosis of abusive head trauma, the presence of hemorrhage on CT scan, and Glasgow Outcome Scale score. Cerebrospinal fluid level of soluble cluster of differentiation 163 was increased in traumatic brain injury patients at t2 versus t1 and controls (median, 95.4 ng/mL [interquartile range, 21.8-134.0 ng/mL] vs 31.0 ng/mL [5.7-77.7 ng/mL] and 27.8 ng/mL [19.1-43.1 ng/mL], respectively; p < 0.05). Cerebrospinal fluid level of ferritin was increased in traumatic brain injury patients at t2 and t1 versus controls (8.3 ng/mL [<7.5-19.8 ng/mL] and 8.9 ng/mL [<7.5-26.7 ng/mL] vs <7.5 ng/mL below lower limit of detection, respectively; p < 0.05). Cerebrospinal fluid levels of soluble interleukin-2 receptor α in traumatic brain injury patients at t2 and t1 were not different versus controls. Multivariate regression revealed associations between high ferritin and age 4 years or younger, lower Glasgow Coma Scale score, abusive head trauma, and unfavorable Glasgow Outcome Scale score.
Children with traumatic brain injury demonstrate evidence for macrophage activation after traumatic brain injury, and in terms of cerebrospinal fluid ferritin, this appears more prominent with young age, initial injury severity, abusive head trauma, and unfavorable outcome. Further study is needed to determine whether biomarkers of macrophage activation may be used to discriminate between aberrant and adaptive immune responses and whether inflammation represents a therapeutic target after traumatic brain injury.
小儿创伤性脑损伤后细胞免疫反应的程度和作用尚不清楚。我们通过分别测量脑脊液中可溶性分化簇163、铁蛋白和可溶性白细胞介素-2受体α的水平，检验了小儿创伤性脑损伤后巨噬细胞/小胶质细胞和T细胞活化的假说，并确定这些生物标志物是否与相关临床变量和预后相关。
对一家成熟的单中心脑脊液库中的样本进行回顾性分析。
一家三级儿童医院的儿科重症监护病房。
66例1个月至16岁的重度创伤性脑损伤（格拉斯哥昏迷量表评分<8）的儿科患者和17例1个月至14岁的对照患者。
无。
在两个时间点（t1 = 17±10小时；t2 = 72±15小时）对每位创伤性脑损伤患者采用酶联免疫吸附测定法测定脑脊液中可溶性分化簇163、铁蛋白和可溶性白细胞介素-2受体α的水平。将创伤性脑损伤后可溶性分化簇163、铁蛋白和可溶性白细胞介素-2受体α的脑脊液水平与对照组进行比较，并分析其与年龄、患者性别、初始格拉斯哥昏迷量表评分、虐待性头部外伤诊断、CT扫描出血情况及格拉斯哥预后量表评分的相关性。创伤性脑损伤患者在t2时的可溶性分化簇163脑脊液水平高于t1时及对照组（中位数分别为95.4 ng/mL[四分位间距，21.8 - 134.0 ng/mL]、31.0 ng/mL[5.7 - 77.7 ng/mL]和27.8 ng/mL[19.1 - 43.1 ng/mL]；p < 0.05）。创伤性脑损伤患者在t2和t1时的铁蛋白脑脊液水平高于对照组（分别为8.3 ng/mL[<7.5 - 19.8 ng/mL]和8.9 ng/mL[<7.5 - 26.7 ng/mL]，而对照组低于检测下限<7.5 ng/mL；p < 0.05）。创伤性脑损伤患者在t2和t1时的可溶性白细胞介素-2受体α脑脊液水平与对照组无差异。多因素回归分析显示，高铁蛋白水平与4岁及以下年龄、较低的格拉斯哥昏迷量表评分、虐待性头部外伤及不良格拉斯哥预后量表评分相关。
创伤性脑损伤患儿在创伤性脑损伤后有巨噬细胞活化的证据，就脑脊液铁蛋白而言，在年幼、初始损伤严重、虐待性头部外伤及预后不良的情况下更为突出。需要进一步研究以确定巨噬细胞活化的生物标志物是否可用于区分异常和适应性免疫反应，以及炎症是否代表创伤性脑损伤后的治疗靶点。
