Myelin Oligodendrocyte Glycoprotein: Deciphering a Target in Inflammatory Demyelinating Diseases.
Myelin Oligodendrocyte Glycoprotein: Deciphering a Target in Inflammatory Demyelinating Diseases.
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DOI：
10.3389/fimmu.2017.00529
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发表时间：
2017
影响因子：
7.3
通讯作者：
Reindl M
中科院分区：
文献类型：
--
作者：
Peschl P;Bradl M;Höftberger R;Berger T;Reindl M
髓鞘少突胶质细胞糖蛋白（Myelin oligodendrocytes glycoprotein， MOG）是免疫球蛋白（immunoglobulin, Ig）超家族成员之一，是一种仅表达于髓鞘和少突胶质细胞膜最外表面的髓鞘蛋白。这使得MOG成为炎症性脱髓鞘疾病中细胞和体液免疫反应的潜在靶点。由于MOG在出生后发育较晚，是少突胶质细胞成熟的重要标志。大约在30年前发现，它是多发性硬化症（MS）的实验性自身免疫模型中研究得最好的自身抗原之一。然而，关于MOG，特别是MOG抗体（Abs）作为ms生物标志物的作用，人类研究产生了有争议的结果，但随着检测方法的改进，使用不同的表达系统检测患者样本中的Abs，这种情况已不再存在。利用重组全长、构象完整的MOG进行细胞检测，最近的几项研究表明，MOG抗体可以在急性弥散性脑脊髓炎（ADEM）、水通道蛋白-4 （AQP4）血清阴性视神经脊髓炎（NMOSD）、单相或复发性孤立性视神经炎（ON）或横断面脊髓炎的主要儿科患者中发现。在非典型MS和n -甲基-d-天冬氨酸受体脑炎重叠脱髓鞘综合征。尽管MOG抗体仅在单相疾病（如ADEM）中短暂观察到，并且其下降与有利的结果相关，但它们在多相ADEM、NMOSD、复发性ON或脊髓炎中持续存在。由于这些疾病的不同临床特征，将MOG抗体阳性病例分类为一种新的疾病实体存在争议。在神经病理学上，MOG抗体的存在以ms典型的脱髓鞘和少突胶质细胞病理为特征，与抗体和补体相关。然而，目前尚不清楚MOG抗体是否仅仅是炎症旁观者效应还是真正的致病作用。本文对MOG抗体的最新进展、临床相关性及其在炎性脱髓鞘疾病的免疫发病机制中的作用提供了更深入的见解。
Myelin oligodendrocyte glycoprotein (MOG), a member of the immunoglobulin (Ig) superfamily, is a myelin protein solely expressed at the outermost surface of myelin sheaths and oligodendrocyte membranes. This makes MOG a potential target of cellular and humoral immune responses in inflammatory demyelinating diseases. Due to its late postnatal developmental expression, MOG is an important marker for oligodendrocyte maturation. Discovered about 30 years ago, it is one of the best-studied autoantigens for experimental autoimmune models for multiple sclerosis (MS). Human studies, however, have yielded controversial results on the role of MOG, especially MOG antibodies (Abs), as a biomarker in MS. But with improved detection methods using different expression systems to detect Abs in patients’ samples, this is meanwhile no longer the case. Using cell-based assays with recombinant full-length, conformationally intact MOG, several recent studies have revealed that MOG Abs can be found in a subset of predominantly pediatric patients with acute disseminated encephalomyelitis (ADEM), aquaporin-4 (AQP4) seronegative neuromyelitis optica spectrum disorders (NMOSD), monophasic or recurrent isolated optic neuritis (ON), or transverse myelitis, in atypical MS and in N-methyl-d-aspartate receptor-encephalitis with overlapping demyelinating syndromes. Whereas MOG Abs are only transiently observed in monophasic diseases such as ADEM and their decline is associated with a favorable outcome, they are persistent in multiphasic ADEM, NMOSD, recurrent ON, or myelitis. Due to distinct clinical features within these diseases it is controversially disputed to classify MOG Ab-positive cases as a new disease entity. Neuropathologically, the presence of MOG Abs is characterized by MS-typical demyelination and oligodendrocyte pathology associated with Abs and complement. However, it remains unclear whether MOG Abs are a mere inflammatory bystander effect or truly pathogenetic. This article provides deeper insight into recent developments, the clinical relevance of MOG Abs and their role in the immunpathogenesis of inflammatory demyelinating disorders.