Zhao Haiping, Li Fangfang, Huang Yuyou, Zhang Sijia, Li Lingzhi, Yang Zhenhong, Wang Rongliang, Tao Zhen, Han Ziping, Fan Junfen, Zheng Yangmin, Ma Qingfeng, Luo Yumin
Cerebrovascular Diseases Research Institute and Department of Neurology, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, China.
Beijing Institute for Brain Disorders, Beijing, China.
J Neuroinflammation. 2020 Aug 14;17(1):237. doi: 10.1186/s12974-020-01920-3.
An imbalance between circulating neuroprotective and neurotoxic T cell subsets leads to poor prognosis in acute ischaemic stroke (AIS). Preclinical studies have indicated that the soluble form of the interleukin-2 receptor α (sIL-2Rα)-IL-2 complex regulates T cell differentiation. However, the association between sIL-2Rα levels and AIS remains unclear.
A total of 201 first-ever AIS patients within 24 h after stroke onset and 76 control subjects were recruited. The National Institutes of Health Stroke Scale (NIHSS) score and 3-month functional outcome (modified Rankin Scale [mRS] score) at admission were assessed. Plasma sIL-2Rα and IL-2 levels at admission were measured. Prognostic significance was identified by using univariate and multivariate logistic regression analyses.
Patients with poor functional outcomes at 3 months had significantly higher levels of sIL-2Rα and lower levels of IL-2 than patients with good outcomes. Moreover, sIL-2Rα levels showed a strong positive correlation with NIHSS and mRS scores (p < 0.0001), whereas IL-2 levels were negatively correlated with mRS scores (p < 0.01). Univariate analyses showed that higher sIL-2Rα and IL-2 levels were associated with an increased and reduced risk of unfavourable outcomes, respectively. After adjusting for confounding variables, the sIL-2Rα level remained independently associated with an increased risk of an unfavourable outcome, and adding sIL-2Rα levels to the conventional risk factor model significantly improved risk reclassification (net reclassification improvement 17.56%, p = 0.003; integrated discrimination improvement 5.78%, p = 0.0003).
sIL-2Rα levels represent a novel, independent prognostic marker that can improve the currently used risk stratification of AIS patients. Our findings also highlight that elevated plasma sIL-2Rα and IL-2 levels manifested opposite correlations with functional outcome, underlining the importance of IL-2/IL-2R autocrine loops in AIS.
循环中的神经保护性T细胞亚群与神经毒性T细胞亚群之间的失衡会导致急性缺血性卒中(AIS)预后不良。临床前研究表明,白细胞介素-2受体α(sIL-2Rα)-白细胞介素-2复合物的可溶性形式可调节T细胞分化。然而,sIL-2Rα水平与AIS之间的关联仍不清楚。
共招募了201例首次发生AIS且在卒中发作后24小时内的患者以及76例对照者。评估了入院时的美国国立卫生研究院卒中量表(NIHSS)评分和3个月功能结局(改良Rankin量表[mRS]评分)。测量了入院时血浆sIL-2Rα和白细胞介素-2水平。通过单因素和多因素逻辑回归分析确定预后意义。
3个月时功能结局较差的患者的sIL-2Rα水平显著高于结局良好的患者,而白细胞介素-2水平则较低。此外,sIL-2Rα水平与NIHSS和mRS评分呈强正相关(p < 0.0001),而白细胞介素-2水平与mRS评分呈负相关(p < 0.01)。单因素分析显示,较高的sIL-2Rα和白细胞介素-2水平分别与不良结局风险增加和降低相关。在调整混杂变量后,sIL-2Rα水平仍与不良结局风险增加独立相关,并且将sIL-2Rα水平添加到传统危险因素模型中可显著改善风险重新分类(净重新分类改善17.56%,p = 0.003;综合判别改善5.78%,p = 0.0003)。
sIL-2Rα水平代表一种新的独立预后标志物,可以改善目前对AIS患者的风险分层。我们的研究结果还突出表明,血浆sIL-2Rα和白细胞介素-2水平升高与功能结局呈相反的相关性,强调白细胞介素-2/白细胞介素-2受体自分泌环在AIS中的重要性。