Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton.
Antibodies to MOG have a demyelination phenotype and affect oligodendrocyte cytoskeleton.
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MOG 抗体具有脱髓鞘表型并影响少突胶质细胞骨架。
DOI：
10.1212/nxi.0000000000000012
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发表时间：
2014-06
期刊：
影响因子：
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通讯作者：
Brilot F
中科院分区：
文献类型：
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作者：
Dale RC;Tantsis EM;Merheb V;Kumaran RY;Sinmaz N;Pathmanandavel K;Ramanathan S;Booth DR;Wienholt LA;Prelog K;Clark DR;Guillemin GJ;Lim CK;Mathey EK;Brilot F
探讨髓鞘少突胶质细胞糖蛋白（MOG）抗体阳性儿童中枢神经系统脱髓鞘的临床特点，并探讨MOG抗体对少突胶质细胞骨架的功能影响。我们对73名患有中枢神经系统脱髓鞘（DEM）的儿童（平均年龄8岁，范围1.3-15.3岁）进行了为期4年的随访，采用荧光活化细胞分选活细胞法检测了他们急性血清中的MOG抗体。我们利用MO3.13细胞三维反褶积成像技术检测免疫球蛋白（Ig） G对少突胶质细胞骨架的影响。73例DEM患者中有31例（42%）存在MOG抗体，对照组中0/24存在MOG抗体。首次出现MOG抗体阳性的患者更容易出现双侧视神经炎（ON）而不是单侧视神经炎（ON）（分别为9/10 vs 1/5， p = 0.03），更不容易出现脑干病变（2/31 vs 16/42, p = 0.005），更不容易出现红细胞沉降率升高（9/19 vs 3/21, p = 0.05），更不容易出现鞘内寡克隆带（0/16 vs 5/27, p = 0.18）。对人白细胞抗原DRB1*1501纯合或杂合的可能性较小（3/18 vs 7/22, p = 0.46）。MOG抗体阳性根据临床表型而变化，ON和复发性ON最有可能呈血清阳性。两名MOG抗体阳性的复发患者接受霉酚酸酯治疗后仍处于缓解期，MOG抗体血清呈阴性。与MOG抗体阳性患者纯化的IgG孵育的少突胶质细胞显示出明显的细丝组织和微管细胞骨架的丢失，f -肌动蛋白和β-微管蛋白免疫标记证明了这一点。MOG抗体可以定义一种单独的脱髓鞘综合征，具有治疗意义。MOG抗体对少突胶质细胞骨架有功能作用。
To examine the clinical features of pediatric CNS demyelination associated with positive myelin oligodendrocyte glycoprotein (MOG) antibodies and to examine the functional effects of MOG antibody on oligodendrocyte cytoskeleton. We measured MOG antibody using a fluorescence-activated cell sorting live cell-based assay in acute sera of 73 children with CNS demyelination (DEM) (median age 8 years, range 1.3–15.3) followed for a median of 4 years. We used MO3.13 cells to examine immunoglobulin (Ig) G effects on oligodendrocyte cytoskeleton using 3D deconvolution imaging. MOG antibodies were found in 31/73 patients with DEM (42%) but in 0/24 controls. At first presentation, MOG antibody–positive patients were more likely to have bilateral than unilateral optic neuritis (ON) (9/10 vs 1/5, respectively, p = 0.03), less likely to have brainstem findings (2/31 vs 16/42, p = 0.005), more likely to have a raised erythrocyte sedimentation rate >20 mm/h (9/19 vs 3/21, p = 0.05), less likely to have intrathecal oligoclonal bands (0/16 vs 5/27, p = 0.18), and less likely to be homozygous or heterozygous for human leukocyte antigen DRB1*1501 (3/18 vs 7/22, p = 0.46). MOG antibody positivity varied according to clinical phenotype, with ON and relapsing ON most likely to be seropositive. Two relapsing MOG antibody–positive patients treated with mycophenolate mofetil remain in remission and have become MOG antibody seronegative. Oligodendrocytes incubated with purified IgG from MOG antibody–positive patients showed a striking loss of organization of the thin filaments and the microtubule cytoskeleton, as evidenced by F-actin and β-tubulin immunolabelings. MOG antibody may define a separate demyelination syndrome, which has therapeutic implications. MOG antibody has functional effects on oligodendrocyte cytoskeleton.