A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury.
A Pilot Study Identifying Brain-Targeting Adaptive Immunity in Pediatric Extracorporeal Membrane Oxygenation Patients With Acquired Brain Injury.
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一项初步研究，旨在识别患有后天性脑损伤的儿科体外膜氧合患者的脑靶向适应性免疫。
DOI：
10.1097/ccm.0000000000003621
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发表时间：
2019
影响因子：
8.8
通讯作者：
Stowe,AnnM
中科院分区：
文献类型：
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作者：
Ortega,SterlingB;Pandiyan,Poornima;Windsor,Jana;Torres,VanessaO;Selvaraj,UmaM;Lee,Amy;Morriss,Michael;Tian,Fenghua;Raman,Lakshmi;Stowe,AnnM
目的：体外膜氧合提供短期心肺生命支持，但与外周先天性炎症、脑自动调节中断和获得性脑损伤相关。我们检验了体外膜氧合也诱导CNS定向的适应性免疫反应的假设，这种免疫反应可能加剧体外膜氧合相关的脑损伤。设计：一项单中心前瞻性观察性研究。设置：在一个三级护理学术中心的儿科和心脏ICU。患者：20例儿科体外膜氧合患者（0-14岁; 13名女性，7名男性）和5名非体外膜肺氧合儿科逻辑器官功能障碍评分匹配的患者干预：无。测量和主要结果：在体外膜氧合的第1天（10-23小时）、第3天和第7天从体外膜氧合回路收集静脉血样。流式细胞术定量循环先天性和适应性免疫细胞，并使用体外回忆反应试验检测CNS-定向自身反应性。使用连续床边近红外光谱测定脑自动调节的中断，并通过MRI证实获得性脑损伤。有获得性脑损伤的体外膜肺氧合患者（n= 9）的白细胞介素-8比无脑损伤的体外膜肺氧合患者增加10倍（p< 0.01）。此外，体外膜肺氧合患者的脑损伤增强了适应性免疫细胞的炎症表型和循环B细胞和细胞毒性T细胞群对脑肽的选择性自身反应性。相关性分析揭示了获得性脑损伤患者的体外膜肺氧合的适应性免疫应答与脑自身调节功能丧失之间的显著关系。
Objectives:Extracorporeal membrane oxygenation provides short-term cardiopulmonary life support, but is associated with peripheral innate inflammation, disruptions in cerebral autoregulation, and acquired brain injury. We tested the hypothesis that extracorporeal membrane oxygenation also induces CNS-directed adaptive immune responses which may exacerbate extracorporeal membrane oxygenation-associated brain injury.Design:A single center prospective observational study.Setting:Pediatric and cardiac ICUs at a single tertiary care, academic center.Patients:Twenty pediatric extracorporeal membrane oxygenation patients (0–14 yr; 13 females, 7 males) and five nonextracorporeal membrane oxygenation Pediatric Logistic Organ Dysfunction score matched patientsInterventions:None.Measurements and Main Results:Venous blood samples were collected from the extracorporeal membrane oxygenation circuit at day 1 (10–23 hr), day 3, and day 7 of extracorporeal membrane oxygenation. Flow cytometry quantified circulating innate and adaptive immune cells, and CNS-directed autoreactivity was detected using an in vitro recall response assay. Disruption of cerebral autoregulation was determined using continuous bedside near-infrared spectroscopy and acquired brain injury confirmed by MRI. Extracorporeal membrane oxygenation patients with acquired brain injury (n= 9) presented with a 10-fold increase in interleukin-8 over extracorporeal membrane oxygenation patients without brain injury (p< 0.01). Furthermore, brain injury within extracorporeal membrane oxygenation patients potentiated an inflammatory phenotype in adaptive immune cells and selective autoreactivity to brain peptides in circulating B cell and cytotoxic T cell populations. Correlation analysis revealed a significant relationship between adaptive immune responses of extracorporeal membrane oxygenation patients with acquired brain injury and loss of cerebral autoregulation.Conclusions: