Identification of circulating MOG-specific B cells in patients with MOG antibodies
Identification of circulating MOG-specific B cells in patients with MOG antibodies
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DOI：
10.1212/nxi.0000000000000625
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发表时间：
2019-11-01
影响因子：
8.8
通讯作者：
Meinl, Edgar
中科院分区：
文献类型：
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作者：
Winklmeier, Stephan;Schlueter, Miriam;Meinl, Edgar
目的鉴定循环髓鞘少突胶质细胞糖蛋白（MOG）特异性B细胞在血液中的MOG抗体（Abs），并确定是否循环MOG特异性B细胞与血清抗MOG抗体的水平和表位特异性。方法我们比较了21例MOG抗体和26例对照的MOG特异性B细胞的存在。我们通过Toll样受体7和8的接合，在体外将单独培养威尔斯孔中的血液来源的B细胞分化为产生Ab的细胞。我们通过流式细胞术用基于活细胞的测定来定量抗MOG反应性。我们确定了MOG表位的识别与MOG.ResultsMOG-Ab-阳性患者的MOG-特异性B细胞在血液中的频率高于对照组，但MOG-特异性B细胞只检测到约60%的这些患者的一个面板的突变的变体。无论是在整个组还是在未经治疗的患者中，血液中MOG特异性B细胞与血清中抗MOG Ab水平均无相关性。MOG-抗体分泌的MOG-特定的B细胞培养在不同的威尔斯的表位分析揭示了一个个体内的抗MOG自身immunity.ConclusionsThis研究表明，患者与MOG-抗体的循环MOG-特定的B细胞，这是不连接到MOG-抗体的血清水平表明不同来源的MOG-抗体的丰度有很大的不同。血液中MOG特异性B细胞的鉴定对于选择具有MOG-Ab的患者进行B细胞定向治疗可能具有未来的相关性。
ObjectiveTo identify circulating myelin oligodendrocyte glycoprotein (MOG)-specific B cells in the blood of patients with MOG antibodies (Abs) and to determine whether circulating MOG-specific B cells are linked to levels and epitope specificity of serum anti-MOG-Abs.MethodsWe compared peripheral blood from 21 patients with MOG-Abs and 26 controls for the presence of MOG-specific B cells. We differentiated blood-derived B cells in vitro in separate culture wells to Ab-producing cells via engagement of Toll-like receptors 7 and 8. We quantified the anti-MOG reactivity with a live cell-based assay by flow cytometry. We determined the recognition of MOG epitopes with a panel of mutated variants of MOG.ResultsMOG-Ab-positive patients had a higher frequency of MOG-specific B cells in blood than controls, but MOG-specific B cells were only detected in about 60% of these patients. MOG-specific B cells in blood showed no correlation with anti-MOG Ab levels in serum, neither in the whole group nor in the untreated patients. Epitope analysis of MOG-Abs secreted from MOG-specific B cells cultured in different wells revealed an intraindividual heterogeneity of the anti-MOG autoimmunity.ConclusionsThis study shows that patients with MOG-Abs greatly differ in the abundance of circulating MOG-specific B cells, which are not linked to levels of MOG-Abs in serum suggesting different sources of MOG-Abs. Identification of MOG-specific B cells in blood could be of future relevance for selecting patients with MOG-Abs for B cell-directed therapy.