Institute for Transplantation Diagnostics and Cell Therapeutics, Heinrich-Heine-University Düsseldorf, 40225, Düsseldorf, Germany.
Medical School, Rheinische Friedrich-Wilhelms University of Bonn, Sigmund Freud Strasse 25, 53121, Bonn, Germany.
BMC Neurol. 2022 May 20;22(1):186. doi: 10.1186/s12883-022-02707-0.
Recent evidence suggests a merging role of immunothrombosis in the formation of arterial thrombosis. Our study aims to investigate its relevance in stroke patients.
We compared the peripheral immunological profile of stroke patients vs. healthy controls. Serum samples were functionally analyzed for their formation and clearance of Neutrophil-Extracellular-Traps. The composition of retrieved thrombi has been immunologically analyzed.
Peripheral blood of stroke patients showed significantly elevated levels of DNAse-I (p < 0.001), LDG (p = 0.003), CD4 (p = 0.005) as well as the pro-inflammatory cytokines IL-17 (p < 0.001), INF-γ (p < 0.001) and IL-22 (p < 0.001) compared to controls, reflecting a T1/T17 response. Increased counts of DNAse-I in sera (p = 0.045) and Neutrophil-Extracellular-Traps in thrombi (p = 0.032) have been observed in patients with onset time of symptoms longer than 4,5 h. Lower values of CD66b in thrombi were independently associated with greater improvement of NIHSS after mechanical thrombectomy (p = 0.045). Stroke-derived neutrophils show higher potential for Neutrophil-Extracellular-Traps formation after stimulation and worse resolution under DNAse-I treatment compared to neutrophils derived from healthy individuals.
Our data provide new insight in the role of activated neutrophils and Neutrophil-Extracellular-Traps in ischemic stroke. Future larger studies are warranted to further investigate the role of immunothrombosis in the cascades of stroke.
DRKS, DRKS00013278, Registered 15 November 2017, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013278.
最近的证据表明，免疫血栓形成在动脉血栓形成中起合并作用。我们的研究旨在探讨其在中风患者中的相关性。
我们比较了中风患者和健康对照组的外周免疫谱。对血清样本进行功能分析，以检测中性粒细胞胞外陷阱的形成和清除。免疫分析了提取血栓的组成。
与对照组相比，中风患者的外周血中 DNAse-I（p<0.001）、LDG（p=0.003）、CD4（p=0.005）以及促炎细胞因子 IL-17（p<0.001）、INF-γ（p<0.001）和 IL-22（p<0.001）水平显著升高，反映了 T1/T17 反应。与症状发作时间超过 4.5 小时的患者相比，血清中 DNAse-I 计数增加（p=0.045）和血栓中中性粒细胞胞外陷阱增加（p=0.032）。血栓中 CD66b 值较低与机械血栓切除术治疗后 NIHSS 评分改善更大独立相关（p=0.045）。与来自健康个体的中性粒细胞相比，中风来源的中性粒细胞在刺激后形成中性粒细胞胞外陷阱的潜力更高，在 DNAse-I 治疗下的分辨率更差。
我们的数据提供了关于激活的中性粒细胞和中性粒细胞胞外陷阱在缺血性中风中的作用的新见解。需要进一步进行更大规模的研究，以进一步探讨免疫血栓形成在中风级联反应中的作用。
DRKS，DRKS00013278，注册于 2017 年 11 月 15 日，https://www.drks.de/drks_web/navigate.do？navigationId=trial.HTML&TRIAL_ID=DRKS00013278。
