Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis
Pattern-specific loss of aquaporin-4 immunoreactivity distinguishes neuromyelitis optica from multiple sclerosis
复制标题
DOI：
10.1093/brain/awl371
复制
发表时间：
2007-05-01
期刊：
影响因子：
14.5
通讯作者：
Lucchinetti, Claudia F.
中科院分区：
文献类型：
--
作者：
Roemer, Shanu F.;Parisi, Joseph E.;Lucchinetti, Claudia F.
视神经脊髓炎（NMO）是一种炎症性脱髓鞘疾病，通常影响视神经和脊髓。其与多发性硬化症（MS）的致病关系尚不确定。与MS不同，NMO病变的特征在于IgG和IgM的沉积物与补体激活产物共定位在增厚的透明化血管周围的血管中心模式中，表明靶向血管周围空间中抗原的体液免疫的致病作用。最近鉴定的特异性血清自身抗体生物标志物NMO-IgG靶向水通道蛋白-4（AQP 4），其是CNS中最丰富的水通道蛋白，其高度集中在星形胶质细胞足突中。我们分析和比较了9例NMO患者、13例MS患者、9例梗死患者和5例正常对照者的CNS组织中AQP 4免疫反应性的模式。在正常脑、视神经和脊髓中，AQP 4表达的分布类似于在NMO病变中观察到的免疫复合物沉积的血管中心模式。与表现出阶段依赖性AQP 4丧失的MS病变相反，所有NMO病变均表现出AQP 4的显著丧失，而不管脱髓鞘活性的阶段、组织坏死的程度或CNS受累的部位。我们确定了一种新的NMO病变在脊髓和髓质被盖延伸到最后区，其特征是AQP 4损失的病灶是炎症和水肿，但既不脱髓鞘也不坏死。AQP 4丢失的病灶与强烈的血管中心性免疫复合物沉积的部位一致。这些发现强烈支持补体激活AQP 4特异性自身抗体作为NMO病变的起始物的作用，并进一步区分NMO和MS。
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that typically affects optic nerves and spinal cord. Its pathogenic relationship to multiple sclerosis (MS) is uncertain. Unlike MS, NMO lesions are characterized by deposits of IgG and IgM co-localizing with products of complement activation in a vasculocentric pattern around thickened hyalinized blood vessels, suggesting a pathogenic role for humoral immunity targeting an antigen in the perivascular space. A recently identified specific serum autoantibody biomarker, NMO-IgG, targets aquaporin-4 (AQP4), the most abundant water channel protein in the CNS, which is highly concentrated in astrocytic foot processes. We analysed and compared patterns of AQP4 immunoreactivity in CNS tissues of nine patients with NMO, 13 with MS, nine with infarcts and five normal controls. In normal brain, optic nerve and spinal cord, the distribution of AQP4 expression resembles the vasculocentric pattern of immune complex deposition observed in NMO lesions. In contrast to MS lesions, which exhibit stage-dependent loss of AQP4, all NMO lesions demonstrate a striking loss of AQP4 regardless of the stage of demyelinating activity, extent of tissue necrosis, or site of CNS involvement. We identified a novel NMO lesion in the spinal cord and medullary tegmentum extending into the area postrema, characterized by AQP4 loss in foci that were inflammatory and oedematous, but neither demyelinated nor necrotic. Foci of AQP4 loss coincided with sites of intense vasculocentric immune complex deposition. These findings strongly support a role for a complement activating AQP4-specific autoantibody as the initiator of the NMO lesion, and further distinguish NMO from MS.