Department of Neurology, High Specialty Medical Unit, Western National Medical Center of the Mexican Institute of Social Security, Guadalajara, Jalisco, Mexico.
Department of Chemistry, University Center of Exact Sciences and Engineering; University of Guadalajara, Guadalajara, Jalisco, Mexico.
Int J Neurosci. 2024 Aug;134(8):826-838. doi: 10.1080/00207454.2022.2153046. Epub 2022 Dec 7.
To review the main pathological findings of Neuromyelitis Optica Spectrum Disorder (NMOSD) associated with the presence of autoantibodies to aquaporin-4 (AQP4) as well as the mechanisms of astrocyte dysfunction and demyelination. An comprehensive search of the literature in the field was carried out using the database of The National Center for Biotechnology Information from . Systematic searches were performed until July 2022. NMOSD is an inflammatory and demyelinating disease of the central nervous system mainly in the areas of the optic nerves and spinal cord, thus explaining mostly the clinical findings. Other areas affected in NMOSD are the brainstem, hypothalamus, and periventricular regions. Relapses in NMOSD are generally severe and patients only partially recover. NMOSD includes clinical conditions where autoantibodies to aquaporin-4 (AQP4-IgG) of astrocytes are detected as well as similar clinical conditions where such antibodies are not detected. AQP4 are channel-forming integral membrane proteins of which AQ4 isoforms are able to aggregate in supramolecular assemblies termed orthogonal arrays of particles (OAP) and are essential in the regulation of water homeostasis and the adequate modulation of neuronal activity and circuitry. AQP4 assembly in orthogonal arrays of particles is essential for AQP4-IgG pathogenicity since AQP4 autoantibodies bind to OAPs with higher affinity than for AQP4 tetramers. NMOSD has a complex background with prominent roles for genes encoding cytokines and cytokine receptors. AQP4 autoantibodies activate the complement-mediated inflammatory demyelination and the ensuing damage to AQP4 water channels, leading to water influx, necrosis and axonal loss. NMOSD as an astrocytopathy is a nosological entity different from multiple sclerosis with its own serological marker: immunoglobulin G-type autoantibodies against the AQP4 protein which elicits a complement-dependent cytotoxicity and neuroinflammation. Some patients with typical manifestations of NMSOD are AQP4 seronegative and myelin oligodendrocyte glycoprotein positive. Thus, the detection of autoantibodies against AQP4 or other autoantibodies is crucial for the correct treatment of the disease and immunosuppressant therapy is the first choice.
综述水通道蛋白 4（AQP4）自身抗体相关的视神经脊髓炎谱系疾病（NMOSD）的主要病理学发现，以及星形胶质细胞功能障碍和脱髓鞘的机制。通过美国国立生物技术信息中心数据库对该领域的文献进行了全面检索。系统检索截至 2022 年 7 月。NMOSD 是一种主要影响视神经和脊髓中枢神经系统的炎症性和脱髓鞘疾病，因此主要解释了临床发现。NMOSD 还会影响脑干、下丘脑和脑室周围区域。NMOSD 的复发通常很严重，患者只能部分恢复。NMOSD 包括检测到星形胶质细胞 AQP4（AQP4-IgG）自身抗体的临床情况以及未检测到此类抗体的类似临床情况。AQP4 是形成通道的完整膜蛋白，其中 AQ4 同工型能够在称为正交排列颗粒（OAP）的超分子组装中聚集，并且对于水动态平衡的调节以及神经元活动和电路的适当调节至关重要。正交排列颗粒中的 AQP4 组装对于 AQP4-IgG 致病性至关重要，因为 AQP4 自身抗体与 OAP 的结合亲和力高于与 AQP4 四聚体的结合亲和力。NMOSD 具有复杂的背景，其中细胞因子和细胞因子受体的基因编码起着重要作用。AQP4 自身抗体激活补体介导的炎症性脱髓鞘，随后损伤 AQP4 水通道，导致水内流、坏死和轴突丢失。作为星形胶质细胞病的 NMOSD 是一种与多发性硬化症不同的疾病实体，具有自身的血清学标志物：针对 AQP4 蛋白的免疫球蛋白 G 型自身抗体，引发补体依赖性细胞毒性和神经炎症。一些具有典型 NMOSOD 表现的患者 AQP4 血清阴性且髓鞘少突胶质细胞糖蛋白阳性。因此，检测针对 AQP4 的自身抗体或其他自身抗体对于正确治疗疾病至关重要，免疫抑制治疗是首选。
