Neuromyelitis optica lesions may inform multiple sclerosis heterogeneity debate
Neuromyelitis optica lesions may inform multiple sclerosis heterogeneity debate
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DOI：
10.1002/ana.23621
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发表时间：
2012-09-01
影响因子：
11.2
通讯作者：
Metz, Imke
中科院分区：
文献类型：
--
作者：
Brueck, Wolfgang;Popescu, Bogdan;Metz, Imke
目的：视神经脊髓炎（NMO）和多发性硬化症（MS）被认为是具有独特病理特征的炎症性脱髓鞘疾病。NMO病理学显示血管周围免疫球蛋白G和补体沉积，以及星形细胞病伴水通道蛋白-4（AQP 4）丢失。MS病变揭示了一个深刻的，个体间异质性的免疫病理学模式的主动脱髓鞘，这已受到挑战的阶段依赖性序列的病理特征的描述。本研究的目的是比较早期活动性脱髓鞘NMO和MS脑病变的组织学特征。方法：对13例脊髓上活动性脱髓鞘NMO进行免疫组化分析。将结果与已发表的MS病变特征进行比较。结果如下：来自AQP 4-IgG血清阳性NMO患者的脊髓上病变亚组揭示了（1）活性脱髓鞘部位巨噬细胞内的补体激活产物和（2）少突胶质细胞凋亡和髓鞘相关糖蛋白的优先损失。这些特征类似于先前与MS病变模式II和III相关的特征，并且除了特征性组织病理学NMO特征（即AQP 4和星形胶质细胞的丢失）之外还存在。释义：早期活动性脱髓鞘NMO病变可能显示出巨噬细胞内的补体和少突胶质细胞凋亡，除了典型的NMO特征外，还与选择性丢失少量髓鞘蛋白有关。我们假设这些发现同时发生在一个子集的活动性脱髓鞘NMO病变。这些观察结果合理地解释了巴内特和Prineas的发现，并进一步支持了MS. ANN NEUROL 2012;72：385394中的个体间异质性概念。
Objective: Neuromyelitis optica (NMO) and multiple sclerosis (MS) are considered inflammatory demyelinating diseases with distinguishing pathological characteristics. NMO pathology shows perivascular immunoglobulin G and complement deposition, as well as an astrocytopathy with aquaporin-4 (AQP4) loss. MS lesions reveal a profound, interindividual heterogeneity in immunopathological patterns of active demyelination, which has been challenged by the description of stage-dependent sequences of pathological features. The aim of our study was to compare the histological characteristics of early active demyelinating NMO and MS brain lesions. Methods: Thirteen cases with supraspinal active demyelinating NMO lesions were analyzed using immunohistochemistry. Results were compared with the published characteristics of MS lesions. Results: A subset of supraspinal lesions from AQP4-IgG-seropositive NMO patients revealed both (1) complement activation products within macrophages at sites of active demyelination and (2) oligodendrocyte apoptosis and a preferential loss of myelin-associated glycoprotein. These characteristics resemble features previously associated with MS lesion patterns II and III, and were present in addition to characteristic histopathological NMO features, namely loss of AQP4 and astrocytes. Interpretation: Early active demyelinating NMO lesions may show complement within macrophages and oligodendrocyte apoptosis associated with a selective loss of minor myelin proteins, in addition to typical NMO features. We hypothesize these findings occur simultaneously only in a subset of active demyelinating NMO lesions. These observations plausibly explain the findings of Barnett and Prineas and further support the concept of interindividual heterogeneity in MS. ANN NEUROL 2012;72:385394.