Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination.
Human antibodies against the myelin oligodendrocyte glycoprotein can cause complement-dependent demyelination.
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DOI：
10.1186/s12974-017-0984-5
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发表时间：
2017-10-25
影响因子：
9.3
通讯作者：
Reindl M
中科院分区：
文献类型：
--
作者：
Peschl P;Schanda K;Zeka B;Given K;Böhm D;Ruprecht K;Saiz A;Lutterotti A;Rostásy K;Höftberger R;Berger T;Macklin W;Lassmann H;Bradl M;Bennett JL;Reindl M
髓鞘少突胶质细胞糖蛋白（MOG）的抗体与中枢神经系统的炎性脱髓鞘疾病的子集相关，如急性播散性脑脊髓炎和视神经肌萎缩谱系障碍。然而，人MOG抗体是致病性的还是附带现象仍然不完全清楚。尽管MOG在哺乳动物中高度保守，但先前的发现显示并非所有人MOG抗体都与啮齿动物MOG结合。因此，我们假设动物模型中人MOG抗体介导的病理可能仅使用物种特异性MOG抗体才明显。我们筛选了80人MOG抗体阳性样品的反应，小鼠和大鼠MOG使用活细胞为基础的测定或免疫组织化学对小鼠，大鼠和人脑组织。随后测试对人MOG或啮齿动物MOG反应的所选样品在鼠器官型脑切片中诱导补体介导的损伤或在刘易斯大鼠的实验性自身免疫性脑炎（EAE）模型中增强脱髓鞘的能力。MOG单克隆抗体8-18-C5用作阳性对照。总体而言，我们发现只有一部分人MOG抗体对小鼠（48/80，60%）或大鼠（14/80，18%）MOG具有反应性。在鼠器官型脑切片上测试来自10名人MOG抗体阳性患者（8/10对小鼠MOG反应，6/10对大鼠MOG反应）、3名人MOG阴性患者和3名健康对照的纯化血清抗体。来自一名患者的纯化IgG具有高滴度的抗人、小鼠和大鼠MOG抗体，并且与髓鞘组织牢固结合，在器官型脑切片中产生显著的补体介导的髓鞘损失，但在EAE模型中没有。单克隆8-18-C5 MOG抗体在器官型脑切片模型和EAE中均引起补体介导的脱髓鞘。该研究显示，人MOG抗体的子集可以在鼠离体动物模型中诱导补体依赖性致病作用。此外，高滴度的物种特异性MOG抗体可能对小鼠和大鼠动物模型中的脱髓鞘作用至关重要。因此，人类MOG抗体的反应性和滴度必须被考虑用于未来的致病性研究。本文的在线版本（10.1186/s12974-017-0984-5）包含补充材料，可供授权用户使用。
Antibodies to the myelin oligodendrocyte glycoprotein (MOG) are associated with a subset of inflammatory demyelinating diseases of the central nervous system such as acute disseminated encephalomyelitis and neuromyelitis optica spectrum disorders. However, whether human MOG antibodies are pathogenic or an epiphenomenon is still not completely clear. Although MOG is highly conserved within mammals, previous findings showed that not all human MOG antibodies bind to rodent MOG. We therefore hypothesized that human MOG antibody-mediated pathology in animal models may only be evident using species-specific MOG antibodies. We screened 80 human MOG antibody-positive samples for their reactivity to mouse and rat MOG using either a live cell-based assay or immunohistochemistry on murine, rat, and human brain tissue. Selected samples reactive to either human MOG or rodent MOG were subsequently tested for their ability to induce complement-mediated damage in murine organotypic brain slices or enhance demyelination in an experimental autoimmune encephalitis (EAE) model in Lewis rats. The MOG monoclonal antibody 8-18-C5 was used as a positive control. Overall, we found that only a subset of human MOG antibodies are reactive to mouse (48/80, 60%) or rat (14/80, 18%) MOG. Purified serum antibodies from 10 human MOG antibody-positive patients (8/10 reactive to mouse MOG, 6/10 reactive to rat MOG), 3 human MOG-negative patients, and 3 healthy controls were tested on murine organotypic brain slices. Purified IgG from one patient with high titers of anti-human, mouse, and rat MOG antibodies and robust binding to myelin tissue produced significant, complement-mediated myelin loss in organotypic brain slices, but not in the EAE model. Monoclonal 8-18-C5 MOG antibody caused complement-mediated demyelination in both the organotypic brain slice model and in EAE. This study shows that a subset of human MOG antibodies can induce complement-dependent pathogenic effects in a murine ex vivo animal model. Moreover, a high titer of species-specific MOG antibodies may be critical for demyelinating effects in mouse and rat animal models. Therefore, both the reactivity and titer of human MOG antibodies must be considered for future pathogenicity studies. The online version of this article (10.1186/s12974-017-0984-5) contains supplementary material, which is available to authorized users.
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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
发表时间：
2014-06
期刊：
Neurology(R) neuroimmunology & neuroinflammation
影响因子：
--
作者：
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Brilot F
DOI：
10.1212/nxi.0000000000000335
发表时间：
2017-05
期刊：
Neurology(R) neuroimmunology & neuroinflammation
影响因子：
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作者：
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通讯作者：
Leypoldt F
DOI：
10.1212/nxi.0000000000000175
发表时间：
2015-12-01
影响因子：
8.8
作者：
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通讯作者：
Berger, Thomas
影响因子：
14.5
作者：
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通讯作者：
COMPSTON, DAS
影响因子：
9.9
作者：
Kitley, Joanna;Woodhall, Mark;Vincent, Angela
通讯作者：
Vincent, Angela