Spectrum of sublytic astrocytopathy in neuromyelitis optica.
Spectrum of sublytic astrocytopathy in neuromyelitis optica.
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视神经脊髓炎的亚溶血性星形细胞病谱。
DOI：
10.1093/brain/awab394
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发表时间：
2022-05-24
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影响因子：
--
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视神经脊髓炎是一种以中枢神经系统星形胶质细胞水孔蛋白-4水通道为靶点的自身免疫性炎症性疾病。迄今为止，视神经脊髓炎中星形细胞病变的组织病理学描述强调了水通道蛋白-4的特征性丧失，伴随着IgG和补体的沉积以及星形细胞的溶解，但亚溶解反应一直被低估。我们对23例视神经脊髓炎尸检病例进行了多模式研究（临床和/或病理证实；337例组织阻滞）。通过评估星形胶质细胞形态、免疫组织化学和AQP4 RNA转录物及其与脱髓鞘活性的关系，我们记录了星形胶质细胞病变的谱，以及补体沉积、小胶质细胞反应、粒细胞浸润和再生活性。在晚期脱髓鞘病变和周围斑块区域，有显著的肥厚性星形胶质细胞增生，比星形胶质细胞溶解更微妙。“营养不良”形态、细胞质空泡化、罗森塔尔纤维和相关的应激蛋白标记表明了退行性成分。在缺乏水通道蛋白-4的亚溶解反应性星形细胞中，AQP4 mRNA转录物的丰度支持igg诱导的水通道蛋白-4内吞/降解后的体内恢复。星形细胞病变扩展到脱髓鞘病变之外，说明星形细胞病是演变中的视神经脊髓炎病变的早期和原发性事件。局灶性星形细胞病变未见水通道蛋白-4丢失或溶解性补体成分沉积，这证实视神经脊髓炎中的星形细胞反应并不仅仅依赖于补体或igg依赖性白细胞介质介导的igg介导的水通道蛋白-4丢失或溶解。我们得出结论，视神经脊髓炎反映了一种全球性的星形细胞病，由IgG与水通道蛋白-4结合引发，而不是简单地通过脱髓鞘和星形细胞溶解来定义。视神经脊髓炎星形细胞形态学变化的频谱证明了影响星形细胞对水通道蛋白-4特异性IgG靶向攻击的生理反应范围的因素的复杂性。亚溶性星形细胞反应无疑是病变演变和修复潜力的重要决定因素。星形细胞应激反应的药理学操作可能为治疗干预提供新的途径。Guo等人描述了视神经脊髓炎中除脱髓鞘病变外的整体胶质下星形细胞变化。代偿性AQP4合成和白细胞增多表明浸润性免疫细胞的内源性修复和限制。与AQP4缺失或补体/白细胞溶解无关的应激反应有利于治疗干预。
Neuromyelitis optica is an autoimmune inflammatory disorder targeting aquaporin-4 water channels in CNS astrocytes. Histopathological descriptions of astrocytic lesions reported in neuromyelitis optica so far have emphasized a characteristic loss of aquaporin-4, with deposition of IgG and complement and lysis of astrocytes, but sublytic reactions have been underappreciated. We performed a multi-modality study of 23 neuromyelitis optica autopsy cases (clinically and/or pathologically confirmed; 337 tissue blocks). By evaluating astrocytic morphology, immunohistochemistry and AQP4 RNA transcripts, and their associations with demyelinating activity, we documented a spectrum of astrocytopathy in addition to complement deposition, microglial reaction, granulocyte infiltration and regenerating activity. Within advanced demyelinating lesions, and in periplaque areas, there was remarkable hypertrophic astrogliosis, more subtle than astrocytic lysis. A degenerative component was suggested by ‘dystrophic’ morphology, cytoplasmic vacuolation, Rosenthal fibres and associated stress protein markers. The abundance of AQP4 mRNA transcripts in sublytic reactive astrocytes devoid of aquaporin-4 protein supported in vivo restoration following IgG-induced aquaporin-4 endocytosis/degradation. Astrocytic alterations extending beyond demyelinating lesions speak to astrocytopathy being an early and primary event in the evolving neuromyelitis optica lesion. Focal astrocytopathy observed without aquaporin-4 loss or lytic complement component deposition verifies that astrocytic reactions in neuromyelitis optica are not solely dependent on IgG-mediated aquaporin-4 loss or lysis by complement or by IgG-dependent leucocyte mediators. We conclude that neuromyelitis optica reflects a global astrocytopathy, initiated by binding of IgG to aquaporin-4 and not simply definable by demyelination and astrocytic lysis. The spectrum of astrocytic morphological changes in neuromyelitis optica attests to the complexity of factors influencing the range of astrocytic physiological responses to a targeted attack by aquaporin-4-specific IgG. Sublytic astrocytic reactions are no doubt an important determinant of the lesion’s evolution and potential for repair. Pharmacological manipulation of the astrocytic stress response may offer new avenues for therapeutic intervention. Guo et al. describe global sublytic astrocytic changes in neuromyelitis optica, beyond demyelinated lesions. Compensatory AQP4 synthesis and leucocyte emperipolesis indicate endogenous repair and restriction of infiltrating immune cells. Stress responses independent of AQP4 loss, or complement/leucocyte lysis, favour therapeutic intervention.
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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：
3.6
作者：
Hwang, Junmo;Vu, Hung M.;Lim, Hyun-Ho
通讯作者：
Lim, Hyun-Ho
DOI：
10.3109/15419069309097256
发表时间：
1993-01-01
期刊：
CELL ADHESION AND COMMUNICATION
影响因子：
--
作者：
FURER, M;HARTLOPER, V;NATH, A
通讯作者：
NATH, A
影响因子：
3.8
作者：
Isobe, I;Maeno, Y;Monma-Ohtaki, J
通讯作者：
Monma-Ohtaki, J
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影响因子：
3.7
作者：
Barcia, Carlos;Sanderson, NicholasS. R.;Barrett, Robert J.;Wawrowsky, Kolja;Kroeger, Kurt M.;Puntel, Mariana;Liu, Chunyan;Castro, Maria G.;Lowenstein, Pedro R.
通讯作者：
Lowenstein, Pedro R.