Holmøy T
Institute of Immunology, Rikshospitalet University Hospital, Faculty of Medicine, University of Oslo, Oslo, Norway.
Minerva Med. 2008 Apr;99(2):119-40.
The disease mechanism of multiple sclerosis (MS) involves inflammation, demyelination and neurodegeneration. The relation between these components is not completely understood, but recent experiences with aggressive anti-inflammatory treatment suggest that inflammation drives neuronal damage in patients with relapsing remitting MS. Although infiltration of lymphocytes into the brain parenchyma was recognized as a key event in the pathogenesis of MS more than 120 years ago, important aspects of the mechanisms triggering and sustaining this immune response remain unknown. Furthermore, studies of MS lesions and evidence from therapeutic trials suggest that the disease mechanism may vary both throughout the disease course and between patients. The understanding of MS as an autoimmune disease targeting myelin proteins is shaped by the animal model experimental autoimmune encephalomyelitis (EAE), but translation from EAE to MS has proven to be difficult. Although both the EAE model and the prominent association to HLA class II molecules suggest a key role for CD4+ T helper cells, it is not known if or how their tolerance to myelin proteins or other putative autoantigens are broken in MS. This paper reviews some important concepts and controversies in the understanding of the immunological basis for MS and its treatment.
多发性硬化症（MS）的发病机制涉及炎症、脱髓鞘和神经变性。这些组成部分之间的关系尚未完全明确，但近期积极抗炎治疗的经验表明，炎症会导致复发缓解型MS患者的神经元损伤。尽管120多年前就已认识到淋巴细胞浸润脑实质是MS发病机制中的关键事件，但引发和维持这种免疫反应的机制的重要方面仍不清楚。此外，对MS病变的研究以及治疗试验的证据表明，疾病机制可能在整个病程中以及患者之间存在差异。将MS理解为一种针对髓鞘蛋白的自身免疫性疾病是基于动物模型实验性自身免疫性脑脊髓炎（EAE），但事实证明从EAE转化到MS是困难的。尽管EAE模型以及与HLA II类分子的显著关联都表明CD4 +辅助性T细胞起关键作用，但在MS中它们对髓鞘蛋白或其他假定自身抗原的耐受性是否被打破以及如何被打破尚不清楚。本文综述了在理解MS免疫基础及其治疗方面的一些重要概念和争议。
