The Walton Centre NHS Foundation Trust, Lower Lane, Fazakerly, Liverpool, UK; The Institute of Infection and Global Health, West Derby Street, University of Liverpool, UK.
Cytokine. 2013 Oct;64(1):90-6. doi: 10.1016/j.cyto.2013.07.019. Epub 2013 Aug 12.
Neuromelitis optica (NMO) is an inflammatory, demyelinating disease of the central nervous system. It is distinguished from multiple sclerosis (MS) by clinical and radiological features and the presence of aquaporin 4 antibodies in approximately 70%. Despite the discovery of these antibodies and the evidence of neutrophils and eosinophils in the CNS parenchyma, the immunopathogenesis of NMO remains poorly understood. Previous studies attempting to assess the role cytokines and chemokines in NMO have primarily been conducted in acute cerebrospinal fluid from East Asian cohorts, have assessed small numbers of mediators in isolation and have not accounted for important confounding factors including antibody status and disease severity. Therefore we conducted a study of a more extensive range of cytokines and associated mediators in post-acute serum from a UK cohort using unsupervised and multivariate analytical techniques to assess the relative concentration of mediators in concert. Our study of 29 patients (aquaporin 4 antibody positive NMO n=19, MS n=10), matched where possible, including for disease severity, has identified and confirmed some key cytokine/chemokine markers in NMO distinct from MS. Our findings shed further light on the importance of specific inflammatory mediators with predominant function in the differentiation, chemotaxis and activity of neutrophils and eosinophils, particularly CCL4, CCL11, granulocyte-colony stimulating factor and myeloperoxidase, and these may represent potential immunomodulatory targets.
视神经脊髓炎(NMO)是一种中枢神经系统的炎症性脱髓鞘疾病。它与多发性硬化症(MS)在临床和影像学特征以及大约 70%的存在水通道蛋白 4 抗体方面有所不同。尽管发现了这些抗体以及中枢神经系统实质中中性粒细胞和嗜酸性粒细胞的存在,但 NMO 的免疫发病机制仍知之甚少。以前试图评估细胞因子和趋化因子在 NMO 中的作用的研究主要是在东亚队列的急性脑脊液中进行的,它们单独评估了少量介质,并且没有考虑到重要的混杂因素,包括抗体状态和疾病严重程度。因此,我们使用无监督和多变量分析技术,在英国队列的急性后期血清中研究了更广泛范围的细胞因子和相关介质,以评估介质的相对浓度。我们对 29 名患者(水通道蛋白 4 抗体阳性 NMO n=19,MS n=10)进行了研究,尽可能进行了匹配,包括疾病严重程度,确定并证实了 NMO 中与 MS 不同的一些关键细胞因子/趋化因子标志物。我们的研究结果进一步说明了特定炎症介质的重要性,这些介质在中性粒细胞和嗜酸性粒细胞的分化、趋化和活性中具有主要功能,特别是 CCL4、CCL11、粒细胞集落刺激因子和髓过氧化物酶,这些可能代表潜在的免疫调节靶点。