The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica.
The pathology of an autoimmune astrocytopathy: lessons learned from neuromyelitis optica.
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DOI：
10.1111/bpa.12099
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Misu T
中科院分区：
文献类型：
--
作者：
Lucchinetti CF;Guo Y;Popescu BF;Fujihara K;Itoyama Y;Misu T
视神经肌炎（NMO）是一种致残性自身免疫性星形细胞病，其特征是典型的严重和复发性视神经炎和视神经广泛性肌萎缩。直到最近，NMO被认为是多发性硬化症（MS）的急性侵袭性变体，尽管早期研究假设NMO和MS可能是两种不同的疾病，具有共同的临床表现。随着高度特异性血清自身抗体（NMO-IgG）的发现，Lennon及其同事提供了第一个明确的证据，将NMO与MS和其他CNS炎性脱髓鞘疾病区分开来。NMO-IgG的靶抗原被证实是水通道蛋白-4（AQP 4），其是中枢神经系统（CNS）中最丰富的水通道蛋白，主要表达于位于血脑屏障的星形胶质细胞足突、软膜下和室管膜下区域。病理学研究表明，星形胶质细胞被选择性地靶向在NMO中的星形胶质细胞蛋白，AQP 4和胶质细胞酸性蛋白（GFAP）的免疫反应性的广泛损失，以及免疫球蛋白的血管周围沉积和补体的激活，甚至在髓鞘相对保存的病变内证明。为了支持这些病理学发现，发现在急性NMO恶化期间脑脊液（CSF）中的GFAP水平显著升高，而MS中CSF-GFAP水平与对照没有实质性差异。此外，最近的实验研究表明，AQP 4抗体是致病性的，导致体外、离体和体内选择性星形胶质细胞破坏和功能障碍。这些发现有力地表明，NMO是一种自身免疫性星形细胞病，其中星形胶质细胞的损伤超过髓鞘和神经元的损伤。本章将回顾最近的神经病理学研究，提供了新的见解的致病机制，细胞目标，以及频谱的组织损伤在NMO。
Neuromyelitis optica (NMO) is a disabling autoimmune astrocytopathy characterized by typically severe and recurrent attacks of optic neuritis and longitudinally-extensive myelitis. Until recently, NMO was considered an acute aggressive variant of multiple sclerosis (MS), despite the fact that early studies postulated that NMO and MS may be two distinct diseases with a common clinical picture. With the discovery of a highly specific serum autoantibody (NMO-IgG), Lennon and colleagues provided the first unequivocal evidence distinguishing NMO from MS and other CNS inflammatory demyelinating disorders. The target antigen of NMO-IgG was confirmed to be aquaporin-4 (AQP4), the most abundant water channel protein in the central nervous system (CNS), mainly expressed on astrocytic foot processes at the blood brain barrier, subpial and subependymal regions. Pathological studies demonstrated that astrocytes were selectively targeted in NMO as evidenced by the extensive loss of immunoreactivities for the astrocytic proteins, AQP4 and glial fibrillary acidic protein (GFAP), as well as perivascular deposition of immunoglobulins and activation of complement even within lesions with a relative preservation of myelin. In support of these pathological findings, GFAP levels in the cerebrospinal fluid (CSF) during acute NMO exacerbations were found to be remarkably elevated in contrast to MS where CSF-GFAP levels did not substantially differ from controls. Additionally, recent experimental studies showed that AQP4 antibody is pathogenic, resulting in selective astrocyte destruction and dysfunction in vitro, ex vivo, and in vivo. These findings strongly suggest that NMO is an autoimmune astrocytopathy where damage to astrocytes exceeds both myelin and neuronal damage. This chapter will review recent neuropathological studies that have provided novel insights into the pathogenic mechanisms, cellular targets, as well as the spectrum of tissue damage in NMO.
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影响因子：
11.2
作者：
Bennett, Jeffrey L.;Lam, Chiwah;Kalluri, Sudhakar Reddy;Saikali, Philippe;Bautista, Katherine;Dupree, Cecily;Glogowska, Magdalena;Case, David;Antel, Jack P.;Owens, Gregory P.;Gilden, Don;Nessler, Stefan;Stadelmann, Christine;Hemmer, Bernhard
通讯作者：
Hemmer, Bernhard
神经霉素炎患者Optica患者的Aquaporin-4结合自身抗体通过下调EAAT2损害谷氨酸的转运。
影响因子：
15.3
作者：
Hinson, Shannon R.;Roemer, Shanu F.;Lucchinetti, Claudia F.;Fryer, James P.;Kryzer, Thomas J.;Chamberlain, Jayne L.;Howe, Charles L.;Pittock, Sean J.;Lennon, Vanda A.
通讯作者：
Lennon, Vanda A.
影响因子：
11.2
作者：
Brueck, Wolfgang;Popescu, Bogdan;Metz, Imke
通讯作者：
Metz, Imke
影响因子：
2.6
作者：
Petelin Gadze Z;Hajnsek S;Basic S;Sporis D;Pavlisa G;Nankovic S
通讯作者：
Nankovic S
DOI：
10.1056/nejmoa0706383
发表时间：
2008-02-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hauser, Stephen L;Waubant, Emmanuelle;Smith, Craig H
通讯作者：
Smith, Craig H