Chihara Norio, Yamamura Takashi
Division of Neurology, Kobe University Graduate School of Medicine, Kobe, Japan.
Department of Immunology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
Semin Immunopathol. 2022 Sep;44(5):599-610. doi: 10.1007/s00281-022-00941-9. Epub 2022 May 30.
Neuromyelitis optica (NMO) is an inflammatory disease that resembles MS in the relapsing clinical course of optic neuritis and myelitis. Two decades of studies have revealed that autoantibodies, reactive to the water channel protein aquaporin 4 (AQP4) are detected in the core group of patients. These autoantibodies play a crucial role in the inflammatory pathology of NMO, involving proinflammatory cytokines, chemokines, and various inflammatory cells such as Th17 cells. Anti-AQP4 antibody-positive NMO differs fundamentally from MS, particularly in the responsiveness to therapies and the neuropathology accompanying destruction of astrocytes. Research into the immunological mechanism has led to the identification of possible targets of therapy, including complement pathway and interleukin-6 (IL-6) receptor signaling. Recent randomized controlled clinical trials have shown the remarkable efficacy of antibodies specific for complement C5, IL-6 receptor, and CD19 B cells in prevention of NMO spectrum disorder relapses, although no such effects were found in anti-AQP4 antibody-negative patients. These results imply that anti-AQP4 antibody is a biomarker predicting the efficacy of therapies, and indicate the future direction towards "precision medicine."
视神经脊髓炎（NMO）是一种炎症性疾病，在视神经炎和脊髓炎的复发临床过程中与多发性硬化症（MS）相似。二十年的研究表明，在核心患者群体中检测到了针对水通道蛋白4（AQP4）的自身抗体。这些自身抗体在NMO的炎症病理过程中起关键作用，涉及促炎细胞因子、趋化因子以及各种炎症细胞，如辅助性T细胞17（Th17细胞）。抗AQP4抗体阳性的NMO与MS有根本区别，特别是在对治疗的反应以及伴随星形胶质细胞破坏的神经病理学方面。对免疫机制的研究已导致确定了可能的治疗靶点，包括补体途径和白细胞介素-6（IL-6）受体信号传导。最近的随机对照临床试验表明，针对补体C5、IL-6受体和CD19 B细胞的特异性抗体在预防NMO谱系障碍复发方面具有显著疗效，尽管在抗AQP4抗体阴性的患者中未发现此类效果。这些结果表明抗AQP4抗体是预测治疗疗效的生物标志物，并指明了“精准医学”的未来方向。
