Multiple sclerosis (MS) is an immune-mediated disease that damages myelin in the central nervous system (CNS). We investigated the profile of CCN3, a known regulator of immune function and a potential mediator of myelin regeneration, in multiple sclerosis in the context of disease state and disease-modifying treatment. CCN3 expression was analysed in plasma, immune cells, CSF and brain tissue of MS patient groups and control subjects by ELISA, western blot, qPCR, histology and in situ hybridization. Plasma CCN3 levels were comparable between collective MS cohorts and controls but were significantly higher in progressive versus relapsing-remitting MS and between patients on interferon-β versus natalizumab. Higher body mass index was associated with higher CCN3 levels in controls as reported previously, but this correlation was absent in MS patients. A significant positive correlation was found between CCN3 levels in matched plasma and CSF of MS patients which was absent in a comparator group of idiopathic intracranial hypertension patients. PBMCs and CD4+ T cells significantly upregulated CCN3 mRNA in MS patients versus controls. In the CNS, CCN3 was detected in neurons, astrocytes and blood vessels. Although overall levels of area immunoreactivity were comparable between non-affected, demyelinated and remyelinated tissue, the profile of expression varied dramatically. This investigation provides the first comprehensive profile of CCN3 expression in MS and provides rationale to determine if CCN3 contributes to neuroimmunological functions in the CNS.

中文翻译：

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CCN3 受多发性硬化症治疗和疾病状态的动态调节


多发性硬化症 (MS) 是一种免疫介导的疾病，会损害中枢神经系统 (CNS) 中的髓磷脂。我们在多发性硬化症的疾病状态和疾病缓解治疗的背景下研究了 CCN3 的概况，CCN3 是一种已知的免疫功能调节剂和髓磷脂再生的潜在介质。通过ELISA、蛋白质印迹、qPCR、组织学和原位杂交分析多发性硬化症患者组和对照受试者的血浆、免疫细胞、脑脊液和脑组织中的CCN3表达。集体 MS 队列和对照组之间的血浆 CCN3 水平相当，但进展型 MS 与复发缓解型 MS 以及使用干扰素-β 的患者与那他珠单抗患者之间的血浆 CCN3 水平显着较高。正如之前报道的，较高的体重指数与对照组较高的 CCN3 水平相关，但在多发性硬化症患者中不存在这种相关性。 MS 患者的匹配血浆和 CSF 中的 CCN3 水平之间发现显着的正相关性，而特发性颅内高压患者的比较组中则不存在这种显着的正相关性。与对照组相比，MS 患者的 PBMC 和 CD4+ T 细胞显着上调 CCN3 mRNA。在中枢神经系统中，在神经元、星形胶质细胞和血管中检测到了 CCN3。尽管未受影响的脱髓鞘组织和髓鞘再生组织之间的区域免疫反应性总体水平相当，但表达谱却存在显着差异。这项研究提供了 MS 中 CCN3 表达的第一个全面概况，并为确定 CCN3 是否有助于 CNS 中的神经免疫功能提供了理论依据。