Sellebjerg F, Jaliashvili I, Christiansen M, Garred P
Department of Neurology, University of Copenhagen, Glostrup Hospital, Denmark.
J Neurol Sci. 1998 May 7;157(2):168-74. doi: 10.1016/s0022-510x(98)00086-0.
The pathogenesis of multiple sclerosis (MS) appears to involve autoimmune phenomena in the central nervous system. Activation of the complement system is suggested to be involved in the pathogenesis.
Cerebrospinal fluid (CSF) and plasma samples from 65 patients with acute optic neuritis (ON) as a possible first symptom of MS (n=18), ON (n=16) or other attacks of clinically definite MS (n=15), and neurological control subjects (n=16) were studied. Activation of the initial part of the complement activation cascade was assessed by measuring activation of the C3 molecule; terminal activation of the complement cascade was assessed by measuring the terminal complement complex (TCC). Demyelination was estimated by the CSF concentration of myelin basic protein and neurological disability was assessed with the Kurtzke expanded disability status scale (EDSS) score.
Activation of the initial part of the complement activation cascade occurred in each of the three groups of patients with demyelinating disease, but was not correlated to demyelination or disability. Increased concentrations of TCC were detected in patients with attacks of MS other than ON. The CSF concentrations of TCC, myelin basic protein (MBP) and neurological disability correlated significantly. The strongest correlation was between neurological disability and the CSF concentration of TCC (r=0.55, P=0.003).
Full activation of the complement cascade during attacks of MS may be restricted to patients with more advanced disease and is significantly correlated to the degree of neurological disability. This suggests that specific treatment with agents that inhibit complement activation may interfere with mechanisms involved in the pathogenesis of neurological disability in patients with MS.
多发性硬化症（MS）的发病机制似乎涉及中枢神经系统的自身免疫现象。补体系统的激活被认为参与了发病过程。
研究了65例急性视神经炎（ON）患者的脑脊液（CSF）和血浆样本，这些患者可能是MS的首发症状（n = 18）、单纯ON（n = 16）或临床确诊MS的其他发作情况（n = 15），以及神经科对照受试者（n = 16）。通过测量C3分子的激活来评估补体激活级联反应初始部分的激活；通过测量末端补体复合物（TCC）来评估补体级联反应的末端激活。通过CSF中髓鞘碱性蛋白的浓度估计脱髓鞘情况，并用Kurtzke扩展残疾状态量表（EDSS）评分评估神经功能障碍。
三组脱髓鞘疾病患者均出现补体激活级联反应初始部分的激活，但与脱髓鞘或残疾无关。在除ON以外的MS发作患者中检测到TCC浓度升高。CSF中TCC、髓鞘碱性蛋白（MBP）的浓度与神经功能障碍显著相关。最强的相关性存在于神经功能障碍与CSF中TCC浓度之间（r = 0.55，P = 0.003）。
MS发作期间补体级联反应的完全激活可能仅限于病情更严重的患者，并且与神经功能障碍的程度显著相关。这表明用抑制补体激活的药物进行特异性治疗可能会干扰MS患者神经功能障碍发病机制中的相关机制。
