Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study.
Complement Profiles in Patients with Amyotrophic Lateral Sclerosis: A Prospective Observational Cohort Study.
复制标题
肌萎缩性侧硬化症患者的补体谱：一项前瞻性观察队列研究。
DOI：
10.2147/jir.s298307
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发表时间：
2021
影响因子：
4.5
通讯作者：
Garred P
中科院分区：
文献类型：
--
作者：
Kjældgaard AL;Pilely K;Olsen KS;Øberg Lauritsen A;Wørlich Pedersen S;Svenstrup K;Karlsborg M;Thagesen H;Blaabjerg M;Theódórsdóttir Á;Gundtoft Elmo E;Torvin Møller A;Pedersen NA;Kirkegaard N;Møller K;Garred P
补体系统被认为参与肌萎缩性侧索硬化症（ALS）的病理生理，ALS是一种进行性运动神经元疾病。在本研究中，我们比较了选定的补体标志物水平与ALS患者的临床结果。这项观察性、探索性队列研究纳入了92名ALS患者、61名疑似动脉瘤性蛛网膜下腔出血的神经系统对照组（NCs）和96名神经系统健康对照组（NHCs）。取外周血和脑脊液（CSF），测定ficolin-1、- 2和- 3；收集素-11、MBL、MASP-3、MAP-1、C4、C3、PTX-3和补体活化产物C4c、C3bc和sC5b-9。我们记录了ALS患者纳入后24至48个月的临床结果，以分析补体标志物对生存时间的影响。与对照组相比，ALS患者血浆中collect -11、C4和sC5b-9升高，CSF中ficolin-3升高。与NHCs相比，ALS患者血浆中Ficolin-2含量显著降低，但与nc相比无显著降低。收集素-11、C3和C3bc浓度与ALS功能评定量表（ALSFRS-R）呈负相关。根据风险比估计，补体标志物水平与生存率之间没有关联。ALS患者表现出凝集素补体通路的特定介质的异常表达以及末端补体通路的激活增加，证实了补体系统可能参与ALS病理生理的观点。
The complement system has been suggested to be involved in the pathophysiology of amyotrophic lateral sclerosis (ALS), a progressive motor neuron disease. In the present study, we compared levels of selected complement markers to clinical outcome in ALS patients. This observational, explorative cohort study included 92 ALS patients, 61 neurological controls (NCs) admitted for suspected aneurysmal subarachnoid haemorrhage, and 96 neurologically healthy controls (NHCs). Peripheral blood and cerebrospinal fluid (CSF) were obtained for the measurement of ficolin-1, −2, and −3; collectin-11, MBL, MASP-3, MAP-1, C4, C3, PTX-3, and complement activation products C4c, C3bc, and sC5b-9. We recorded clinical outcomes of ALS patients for 24 to 48 months after inclusion in order to analyse the effects of the complement markers on survival time. Compared with both control groups, ALS patients exhibited increased collectin-11, C4 and sC5b-9 in plasma, as well as increased ficolin-3 in CSF. Ficolin-2 was significantly decreased in plasma of the ALS patients compared with NHCs, but not with NCs. The concentration of collectin-11, C3 and C3bc correlated negatively with the revised ALS functional rating scale (ALSFRS-R). No association was found between levels of complement markers and survival as estimated by hazard ratios. ALS patients exhibit aberrant expression of selected mediators of the lectin complement pathway as well as increased activation of the terminal complement pathway, corroborating the notion that the complement system might be involved in the pathophysiology of ALS.