Autoimmunity in neuromyelitis optica and opticospinal multiple sclerosis: Astrocytopathy as a common denominator in demyelinating disorders
Autoimmunity in neuromyelitis optica and opticospinal multiple sclerosis: Astrocytopathy as a common denominator in demyelinating disorders
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DOI：
10.1016/j.jns.2011.08.043
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发表时间：
2011-12-15
影响因子：
4.4
通讯作者：
Kira, Jun-ichi
中科院分区：
文献类型：
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作者：
Kira, Jun-ichi
视神经脊髓炎（NMO）选择性影响视神经和脊髓。在亚洲，多发性硬化症（MS）很少见；然而，当它出现时，视神经和脊髓的选择性和严重受累是典型的。这种形式被称为视脊髓多发性硬化症（OSMS），与西方人的NMO复发形式具有相似的特征。NMO-IgG（一种NMO特异性IgG）靶向水通道蛋白-4 (AQP4)，这一发现表明NMO是一种独特的疾病实体，其病因与ms根本不同。因为NMO-IgG存在于30-60%的OSMS患者中，亚洲人的OSMS被认为是与NMO相同的实体。在病理学上，血管周围免疫复合物（IgM、IgG和C9neo）的沉积和AQP4的广泛丢失是活动性病变的标志。然而，我们发现一些尸检的NMO病例显示选择性AQP4丢失，而其他病例显示AQP4保存，尽管广泛的组织破坏。补体和免疫球蛋白的血管中心沉积仅在NMO患者中检测到，不到30%的活动性脱髓鞘病变显示AQP4丢失。这种AQP4表达和免疫球蛋白沉积的异质性提示NMO的疾病过程具有异质性。我们最近报道了在Balo病（MS的一种变体）活跃性脱髓鞘病变的脱髓鞘层和髓鞘层中，AQP4在胶质原纤维酸性蛋白阳性的肥大星形胶质细胞中广泛丢失。我们还发现，在一些急性MS病变中，AQP4的广泛丢失远远超出了髓鞘丢失的范围。活动性脱髓鞘病变涉及血管周围淋巴细胞，在Balo病和MS中主要由T细胞组成，而在NMO中大约一半的活动性病变也是如此。本综述认为，抗AQP4抗体依赖性的AQP4丢失发生在一些NMO患者中，而非抗体依赖性的AQP4星形细胞病可发生在异质脱髓鞘疾病中，包括Balo病、NMO和ms，后者可能由T细胞和其他细胞介导的机制介导，应在未来的实验研究中进行验证。(C) 2011 Elsevier B.V.版权所有
Neuromyelitis optica (NMO) selectively affects the optic nerves and spinal cord. In Asians, multiple sclerosis (MS) is rare; however, when it appears, the selective and severe involvement of the optic nerves and spinal cord is characteristic. This form, termed opticospinal multiple sclerosis (OSMS), has similar features to the relapsing form of NMO in Westerners. The discovery that NMO-IgG, an NMO-specific IgG, targets aquaporin-4 (AQP4), suggested that NMO is a distinct disease entity with a fundamentally different etiology from MS. Because NMO-IgG is present in 30-60% of OSMS patients, OSMS in Asians is suggested to be the same entity as NMO. Pathologically, perivascular immune complex (IgM, IgG and C9neo) deposition and extensive loss of AQP4 in active lesions are reported hallmarks of NMO. However, we found that some autopsied NMO cases showed selective AQP4 loss while others showed preservation of AQP4, despite extensive tissue destruction. Vasculocentric deposition of complement and immunoglobulin was detected only in NMO patients, with less than 30% of actively demyelinating lesions showing AQP4 loss. Such heterogeneity of AQP4 expression and immunoglobulin deposition suggests a heterogeneous disease process in NMO. We recently reported that AQP4 was extensively lost in glial fibrillary acidic protein-positive hypertrophic astrocytes, both in demyelinated and myelinated layers of actively demyelinating lesions in Balo's disease, a variant of MS. We also found that in some acute MS lesions, AQP4 was lost extensively far beyond the areas of myelin loss. Active demyelinating lesions involved perivascular lymphocyte cuffings, consisting mainly of T cells in Balo's disease and MS, while the same was true for approximately half of the active lesions in NMO. This review proposes that anti-AQP4 antibody-dependent AQP4 loss occurs in some NMO patients while antibody-independent AQP4 astrocytopathy can occur in heterogeneous demyelinating conditions, including Balo's disease, NMO and MS. The latter may be mediated by T cells and other cell-mediated mechanisms, and should be tested in future experimental studies. (C) 2011 Elsevier B.V. All rights reserved.