Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica.
Presence of six different lesion types suggests diverse mechanisms of tissue injury in neuromyelitis optica.
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DOI：
10.1007/s00401-013-1116-7
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发表时间：
2013-06
影响因子：
12.7
通讯作者：
Lassmann H
中科院分区：
文献类型：
--
作者：
Misu T;Höftberger R;Fujihara K;Wimmer I;Takai Y;Nishiyama S;Nakashima I;Konno H;Bradl M;Garzuly F;Itoyama Y;Aoki M;Lassmann H
视神经脊髓炎 (NMO) 是一种针对水通道蛋白 4 (AQP4) 的自身免疫性疾病，主要位于星形细胞足突。据报道，AQP4 和胶质纤维酸性蛋白 (GFAP) 缺失，但星形细胞病的病理意义仍存在争议。在这里，我们表明，即使在个体患者的单个组织块内，NMO 中的活动性病变也显示出广泛的病理学。我们区分了六种不同的病变类型。第一个反映了星形胶质细胞表面的补体沉积，与粒细胞浸润和星形胶质细胞坏死相关，然后是脱髓鞘、整体组织破坏和囊性坏死病变（病变类型2）的形成。这种破坏性病变导致病变相关束的华勒变性（病变类型 3）。在活动性 NMO 病变周围，在没有水通道蛋白 1 (AQP1) 丢失或其他结构损伤的情况下，AQP4 可能会选择性丢失（病变类型 4）。另一种模式的特征是星形胶质细胞的纤枝树病，其定义为细胞质肿胀和空泡形成、其突起的成珠和溶解以及类似于细胞凋亡的核改变，这与 AQP4 和 AQP1 的内化以及在补体激活不存在的情况下星形胶质细胞凋亡有关。此类病变会导致星形胶质细胞广泛损失，部分情况下可能会在没有任何其他组织损伤的情况下发生，例如脱髓鞘或轴突变性（病变类型 5）。最后，发现了具有不同程度的星形胶质细胞纤毛病的病变，其显示出与少突胶质细胞凋亡相关的斑块状原发性脱髓鞘，但与轴突的保存有关（病变类型6）。在活动性多发性硬化症 (MS) 病变中，星形胶质细胞显示反应性原生质或纤维神经胶质增生的变化。仅在患有侵袭性疾病的患者的一部分病变中，在其形成的初始阶段观察到 AQP4 的丢失，这与在没有补体沉积、粒细胞浸润或 AQP1 或星形胶质细胞丢失的情况下星形胶质细胞过程的回缩有关。我们的数据强调了星形胶质细胞在 NMO 病变中的主要攻击，但也表明不同的组织损伤机制在同一患者甚至同一病变内并行运作。本文的在线版本 (doi:10.1007/s00401-013-1116-7) 包含补充材料，可供授权用户使用。
Neuromyelitis optica (NMO) is an autoimmune disease targeting aquaporin 4 (AQP4), localized mainly at the astrocytic foot processes. Loss of AQP4 and glial fibrillary acidic protein (GFAP) was reported, but the pathological significance of astrocytopathy is still controversial. Here we show that active lesions in NMO display a wide spectrum of pathology even within a single tissue block of an individual patient. We have distinguished six different lesion types. The first reflects complement deposition at the surface of astrocytes, associated with granulocyte infiltration and astrocyte necrosis and followed by demyelination, global tissue destruction and the formation of cystic, necrotic lesions (lesion type 2). Such destructive lesions lead to Wallerian degeneration in lesion-related tracts (lesion type 3). Around active NMO lesions AQP4 may selectively be lost in the absence of aquaporin 1 (AQP1) loss or other structural damage (lesion type 4). Another pattern is characterized by clasmatodendrosis of astrocytes, defined by cytoplasmic swelling and vacuolation, beading and dissolution of their processes and nuclear alterations resembling apoptosis, which was associated with internalization of AQP4 and AQP1 and astrocyte apoptosis in the absence of complement activation. Such lesions give rise to extensive astrocyte loss, which may occur in part in the absence of any other tissue injury, such as demyelination or axonal degeneration (lesion type 5). Finally, lesions with a variable degree of astrocyte clasmatodendrosis are found, which show plaque-like primary demyelination that is associated with oligodendrocyte apoptosis, but with preservation of axons (lesion type 6). In active multiple sclerosis (MS) lesions astrocytes reveal changes of reactive protoplasmatic or fibrillary gliosis. Only in a subset of lesions, in patients with aggressive disease, loss of AQP4 is observed in the initial stage of their formation, which is associated with retraction of astrocyte processes in the absence of complement deposition, granulocyte infiltration or loss of AQP1 or astrocytes. Our data underline the primary assault of astrocytes in NMO lesions, but also indicate that different mechanisms of tissue injury operate in parallel in the same patient and even within the same lesion. The online version of this article (doi:10.1007/s00401-013-1116-7) contains supplementary material, which is available to authorized users.
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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：
2.9
作者：
Gelot, Antoinette;Villapol, S.;Charriaut-Marlangue, Christiane
通讯作者：
Charriaut-Marlangue, Christiane
影响因子：
6.4
作者：
Lassmann, Hans;Brueck, Wolfgang;Lucchinetti, Claudia F.
通讯作者：
Lucchinetti, Claudia F.