In multiple sclerosis (MS), the inflammation and demyelination of the central nervous system (CNS) develop in distinct ways. This makes diagnosing patients difficult, imperative to initiating early and proper treatment. Several common features exist, among them a profound infiltration of monocytes into the CNS mediating demyelination and tissue destruction. In the periphery, monocytes are divided into three subsets depending on expression of CD14 and CD16, representing different stages of activation and differentiation. To investigate their involvement in MS, peripheral blood mononuclear cells (PBMCs) from 61 patients with incipient, untreated MS and 22 symptomatic control (SC) patients as well as 6 patients with radiologically isolated syndrome (RIS) were characterized ex vivo . In addition, paired serum and cerebrospinal fluid (CSF) samples were analyzed with a panel of biomarkers. In PBMC samples, we demonstrate decreased levels of nonclassical monocytes with a concomitant significant decrease of human endogenous retrovirus (HERV) H3 envelope epitopes on this monocyte subset compared with SC and RIS. The observed HERV expression is present on nonclassical monocytes irrespective of MS and thus presumably a result of the inflammatory activation. For the other surface markers analyzed, we found significantly decreased expression between classical and nonclassical monocytes. In matched samples of CSF a highly significant increase in levels of soluble markers of activation and inflammation is shown, and notably this is not the case for the serum samples. Of the soluble markers investigated, interleukin (IL)‐12/IL‐23p40 had the highest discriminatory power in differentiating patients with MS from SC and RIS, almost comparable to the immunoglobulin G index.

中文翻译：

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新诊断的多发性硬化症中活化的单核细胞和炎症标志物

在多发性硬化症（MS）中，中枢神经系统（CNS）的炎症和脱髓鞘以不同的方式发展。这使诊断患者变得困难，必须尽早开始适当的治疗。存在几个共同的特征，其中单核细胞深入渗透到CNS中，介导脱髓鞘和组织破坏。在外周，根据CD14和CD16的表达，单核细胞分为三个子集，分别代表激活和分化的不同阶段。为了研究它们在MS，外周血单核细胞从61例初期，未经处理的MS和22对症控制（SC）的患者（PBMC）中的参与以及6例放射学孤立综合征（RIS）进行了表征体外。此外，配对的血清和脑脊液（CSF）样品用一组生物标志物进行了分析。在PBMC样本中，我们证明了与SC和RIS相比，非经典单核细胞的水平降低，与此单核细胞子集上的人类内源性逆转录病毒（HERV）H3包膜表位显着降低。不论MS如何，观察到的HERV表达都存在于非经典单核细胞上，因此推测是炎症激活的结果。对于分析的其他表面标记，我们发现经典和非经典单核细胞之间的表达明显降低。在匹配的CSF样品中，显示出激活和炎症的可溶性标记物水平显着增加，尤其是血清样品并非如此。在研究的可溶性标记物中，