中重度急性缺血性卒中患者的系统性S100A8/A9：炎症和功能结局的探索性分析

IF 3.7 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health Pub Date : 2025-06-18 DOI:10.1016/j.bbih.2025.101041

Christoph Vollmuth , Felipe A. Montellano , Cornelia Fiessler , Fabian Essig , Christian Hametner , Alexander M. Kollikowski , Vivian Vogt , Mirko Pham , Peter U. Heuschmann , Karl Georg Haeusler , Guido Stoll , Hermann Neugebauer , Michael K. Schuhmann

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引用次数: 0

摘要

s100a8 /A9是一种危险相关分子模式（DAMP），从白细胞（主要是中性粒细胞）释放，并增加炎症和组织损伤。全身血浆中S100A8/A9水平在卒中相关炎症中的作用及其与临床结局的关系缺乏足够的数据。方法前瞻性、单中心、观察性研究，纳入中度至重度急性缺血性前循环卒中患者[美国国立卫生研究院卒中量表（NIHSS）评分≥6分和/或机械再通]。我们在脑卒中后3个月（±14天）通过电话访谈评估功能预后，采用改良的7分Rankin量表（mRS）。预后不良定义为mRS≥3。在症状出现48小时后，通过ELISA检测全身血浆中S100A8/A9的水平，同时检测差异血细胞计数。采用单变量和多变量logistic回归研究全身血浆S100A8/A9水平与功能结局之间的关系。结果2020年6月至2022年9月，共纳入272例患者[52%为女性，中位年龄79岁（IQR: 66-84），入院时NIHSS评分中位数为13 (IQR: 8 - 17)，中位ASPECTS评分为8 (IQR: 6-9)]。其中，220名患者（81%）接受了机械再通，118名患者（43%）接受了全身溶栓治疗。血浆S100A8/A9水平与基线中性粒细胞计数之间存在显著相关性[p <；0.0001;R = 0.33(95%置信区间：0.22；0.44)]。在3个月时，272例患者中有192例（71%）功能预后较差，他们在基线时全身血浆中S100A8/A9水平显著高于功能预后良好的患者[中位数：525 ng/ml (IQR: 342-897)]；p = 0.001]。此外，基线时全身血浆S100A8/A9水平与不良预后相关[未经调整的优势比（OR）： 2.01 (95% CI: 1.04-3.96)]，然而，当调整年龄、性别、入院时NIHSS评分、入院时ASPECT评分和再通治疗（是/否）时，这种关联减弱，不再显著[调整的OR: 1.92 (95% CI: 0.86-4.34)]。结论血浆S100A8/A9水平与中重度缺血性脑卒中患者预后不良相关。观察到的与基线中性粒细胞计数的相关性可能强调了患者预后与卒中相关炎症之间的重要病理生理联系。研究registrationDRKS00022064。

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Systemic S100A8/A9 in patients with moderate to severe acute ischemic stroke: Exploratory analysis of inflammation and functional outcome

Introduction

S100A8/A9, a danger-associated molecular pattern (DAMP), is released from leukocytes, mainly neutrophils, and augments inflammation and tissue damage. The role of systemic plasma levels of S100A8/A9 in stroke-related inflammation and its association with clinical outcome lacks sufficient data.

Methods

Prospective, monocentric, observational study including patients with moderate to severe acute ischemic anterior circulation stroke [National Institutes of Health Stroke Scale (NIHSS) score ≥6 points and/or mechanical recanalization)]. We assessed functional outcome by telephone interview 3 months (±14 days) after stroke using the 7-point modified Rankin Scale (mRS). Poor outcome was defined as mRS ≥3. Systemic plasma levels of S100A8/A9 were determined by ELISA <48 h after onset of symptoms, alongside a differential blood count. Univariable and multivariable logistic regression were performed to investigate the association between systemic plasma levels of S100A8/A9 and functional outcome.

Results

Between June 2020 and September 2022, a total of 272 patients were enrolled [52 % female, median age 79 years (IQR: 66–84), median NIHSS score on admission 13 (IQR: 8–17), median ASPECTS 8 (IQR: 6–9)]. Of these, 220 patients (81 %) underwent mechanical recanalization, and 118 (43 %) received systemic thrombolytic therapy. There was a significant correlation between systemic plasma levels of S100A8/A9 and neutrophil counts at baseline [p < 0.0001; r = 0.33 (95 % confidence interval: 0.22; 0.44)]. At 3 months, 192 of 272 (71 %) patients had poor functional outcome, who had significantly higher systemic plasma levels of S100A8/A9 at baseline [median: 525 ng/ml (IQR: 342–897)] than those with good functional outcome [397 ng/ml (IQR: 232–580); p = 0.001]. Furthermore, systemic plasma levels of S100A8/A9 at baseline were associated with poor outcome [unadjusted odds ratio (OR): 2.01 (95 %CI: 1.04–3.96)], however this association was attenuated and no longer significant when adjusting for age, sex, NIHSS Score on admission, ASPECT Score on admission and recanalization therapy (yes/no) [adjusted OR: 1.92 (95 %CI: 0.86–4.34)].

Conclusions

Systemic plasma levels of S100A8/A9 were associated with poor outcome in patients with moderate to severe ischemic stroke. The observed correlation with neutrophil counts at baseline might underscore an important pathophysiological link between patients’ prognosis and stroke-related inflammation.