Loss of aquaporin-4 in active perivascular lesions in neuromyelitis optica: A case report
Loss of aquaporin-4 in active perivascular lesions in neuromyelitis optica: A case report
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DOI：
10.1620/tjem.209.269
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发表时间：
2006-07-01
影响因子：
2.2
通讯作者：
Itoyama, Yasuto
中科院分区：
文献类型：
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作者：
Misu, Tatsuro;Fujihara, Kazuo;Itoyama, Yasuto
视神经脊髓炎(NMO)的临床特征是严重的视神经炎和横贯性脊髓炎。在日本，NMO被命名为视髓多发性硬化症(OSMS)，被认为是多发性硬化症(MS)的一个亚型。然而，一些临床和实验室研究表明，NMO或OSM不同于MS。最近，在NMO患者的血清中发现了疾病特异性抗体(NMO-Ig G)，其靶抗原被鉴定为水通道蛋白4(AQP4)，主要表达于星形胶质细胞足突。然而，AQP4在NMO中的致病作用尚不清楚。我们在此报告一个典型的NMO病例，免疫组织化学分析显示脊髓病变中缺少AQP4。AQP4在中央灰质丢失明显，尤其是血管周围沉积免疫球蛋白和补体的病变，胶质纤维酸性蛋白(GFAP)染色较弱。然而，GFAP在病变周围的反应性星形胶质细胞增生处呈强阳性染色。髓鞘碱性蛋白(MBP)染色的有髓纤维在AQP4缺失的病灶中相对保存。与这些NMO损伤相比，AQP4主要在对照脊髓的灰质表达，而在脱髓鞘的MS损伤中AQP4仍有表达。我们的研究结果表明，与AQP4体液免疫相关的星形细胞损伤可能是NMO病变形成的主要原因，NMO的发病机制不同于以脱髓鞘为主要病理改变的MS。-视神经脊髓炎；视脊髓多发性硬化症；水通道蛋白4；脱髓鞘；星形胶质细胞(C)2006东北大学医科出版社
Neuromyelitis optica (NMO) is clinically characterized by severe optic neuritis and transverse myelitis. In Japan, NMO has been named optic-spinal multiple sclerosis (OSMS) and it has been thought to be a subtype of multiple sclerosis (MS). However, several clinical and laboratory findings suggest NMO or OSMS is distinct from MS. Recently, the disease-specific antibody (NMO-IgG) was found in the serum from NMO patients, and its target antigen was identified as aquaporin-4 (AQP4) water channel protein which is mainly expressed in astroglial foot processes. However, the pathogenetic role of AQP4 in NMO remains unknown. We herein report a typical case of NMO in which immunohistochemical analysis showed a lack of AQP4 in the spinal cord lesions. The loss of AQP4 was evident in the central gray matter, especially in the perivascular lesions where immunoglobulins and complements were deposited, and glial fibrillary acidic protein (GFAP) staining was weak in those lesions. However, GFAP was strongly stained at the reactive astrogliosis surrounding the lesions. Myelin basic protein (MBP)-stained myelinated fibers were relatively preserved in the lesions where AQP4 was lost. In contrast to these NMO lesions, AQP4 was expressed predominantly in the gray matter in control spinal cords, and AQP4 was preserved in demyelinating MS lesions. Our findings suggest that astrocytic impairment associated with humoral immunity against AQP4 may be primarily involved in the lesion formation of NMO, and that the pathomechanisms of NMO are different from those of MS in which demyelination is the primary pathology. - neuromyelitis optica; optic-spinal multiple sclerosis; aquaporin 4; demyelination; astroglia (c) 2006 Tohoku University Medical Press