目的:已知补体系统在多发性硬化症(MS)的发病机理中起作用。然而,它对疾病进展的贡献仍然难以捉摸。该研究调查了补体系统在原发性进行性MS(PPMS)患者残疾进展中的作用。
方法:研究纳入了来自12个欧洲MS中心的68例PPMS患者。在基线时间点通过多重酶联免疫吸附测定测量一组补体成分(CC)的血清和CSF水平(即,sampling).从基线开始的平均(SD)随访时间为9.6(4.8)年。随访期间只有1例患者(1.5%)接受治疗。单变量和多变量逻辑回归调整年龄,性别,和白蛋白商评估基线CC水平与短期(2年)残疾进展之间的关系,中期(6年),和长期(在最后一次随访时)。
结果:在短期内,CC在残疾进展中几乎没有或根本没有作用。从中期来看,血清C3a/C3比值升高与更高的残疾进展风险相关(校正OR2.30;95%CI1.17~6.03;p=0.040).相比之下,CSFC1q水平升高与残疾进展风险降低趋势相关(校正OR0.43;95%CI0.17-0.98;p=0.054).同样,从长远来看,血清C3a/C3比值升高与更高的残疾进展风险相关(校正OR1.81;95%CI1.09-3.40;p=0.037),CSFC1q水平升高可预测残疾进展降低(校正OR0.41;95%CI0.17-0.86;p=0.025)。
结论:参与早期补体级联激活的蛋白质在PPMS患者随访6年或更长时间后作为风险因素(血清C3a/C3比值升高)或保护性因素(CSFC1q升高)在残疾进展中起作用。与CSF中C1q水平相关的保护作用可能与其神经保护和抗炎特性有关。
OBJECTIVE: The complement system is known to play a role in multiple sclerosis (MS) pathogenesis. However, its contribution to disease progression remains elusive. The study investigated the role of the complement system in disability progression of patients with primary progressive MS (PPMS).
METHODS: Sixty-eight patients with PPMS from 12 European MS centers were included in the study. Serum and CSF levels of a panel of complement components (CCs) were measured by multiplex enzyme-linked immunosorbent assay at a baseline time point (i.e., sampling). Mean (SD) follow-up time from baseline was 9.6 (4.8) years. Only one patient (1.5%) was treated during follow-up. Univariable and multivariable logistic regressions adjusted for age, sex, and albumin quotient were performed to assess the association between baseline CC levels and disability progression in short term (2 years), medium term (6 years), and long term (at the time of the last follow-up).
RESULTS: In short term, CC played little or no role in disability progression. In medium term, an elevated serum C3a/C3 ratio was associated with a higher risk of disability progression (adjusted OR 2.30; 95% CI 1.17-6.03; p = 0.040). By contrast, increased CSF C1q levels were associated with a trend toward reduced risk of disability progression (adjusted OR 0.43; 95% CI 0.17-0.98; p = 0.054). Similarly, in long term, an elevated serum C3a/C3 ratio was associated with higher risk of disability progression (adjusted OR 1.81; 95% CI 1.09-3.40; p = 0.037), and increased CSF C1q levels predicted lower disability progression (adjusted OR 0.41; 95% CI 0.17-0.86; p = 0.025).
CONCLUSIONS: Proteins involved in the activation of early complement cascades play a role in disability progression as risk (elevated serum C3a/C3 ratio) or protective (elevated CSF C1q) factors after 6 or more years of follow-up in patients with PPMS. The protective effects associated with C1q levels in CSF may be related to its neuroprotective and anti-inflammatory properties.