Kawamoto Eiji, Nakahashi Susumu, Okamoto Takayuki, Imai Hiroshi, Shimaoka Motomu
Emergency and Critical Care Center, Mie University Hospital, 2-174 Edobashi, Tsu 514-8507, Japan.
Autoimmune Dis. 2012;2012:357101. doi: 10.1155/2012/357101. Epub 2012 Dec 17.
Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin.
整合素是调节健康和疾病状态下免疫细胞迁移的首要细胞黏附分子家族。整合素α4介导免疫细胞向炎症大脑的器官特异性迁移，从而在多发性硬化症的发病机制中发挥关键作用。旨在阻止自身反应性淋巴细胞浸润到炎症大脑的抗α4整合素疗法已在多项治疗多发性硬化症的临床试验中得到验证。本文为读者提供了整合素激活的分子和结构基础概述，以及使用抗α4整合素疗法治疗多发性硬化症的理论依据，然后记述了使用人源化抗α4整合素那他珠单抗的这一治疗策略的兴衰。
