From the IRCCS-Istituto di Ricerche Farmacologiche Mario Negri (E.R.Z., R.Z., F.O., M.T., M.-G.D.S.), Department of Neuroscience, Milan; Department of Physiopathology and Transplant, Milan University and Neuro ICU (R.Z., T.Z., V.C., N.S.), Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy; and Laboratory of Molecular Medicine (L.M.-F., E.H., P.G.), Department of Clinical Immunology, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark.
Neurology. 2014 Jan 14;82(2):126-34. doi: 10.1212/WNL.0000000000000020. Epub 2013 Dec 11.
To assess the involvement of ficolin-3, the main initiator of the lectin complement pathway (LCP), in subarachnoid hemorrhage (SAH) pathology and outcome.
In this preliminary exploratory study, plasma concentration of ficolin-3 and of ficolin-3-mediated functional LCP activity was measured, along with that of other LCP initiators (mannose-binding lectin, ficolin-2, and ficolin-1), C3 activation products, and soluble C5b-9 terminal complex, in a prospective cohort of 39 patients with SAH and 20 healthy controls. The following parameters were recorded: SAH severity, assessed using the World Federation of Neurosurgical Societies grading scale; vasospasm, defined as neuro-worsening with angiographic confirmation of vessel narrowing; cerebral ischemia, defined as hypodense lesion on CT scan performed before discharge; and 6-month outcome, assessed using the Glasgow Outcome Scale.
In patients, no changes were detected for ficolin-3 compared with controls. Notably, however, ficolin-3-mediated functional LCP activity was reduced. Low levels of plasma ficolin-3 and ficolin-3-mediated functional LCP activity were related to SAH severity, vasospasm, and cerebral ischemia. Moreover, ficolin-3 functional LCP activity was decreased in patients with unfavorable outcome.
Our data provide evidence that LCP is activated after SAH and that the actual plasma concentrations of ficolin-3 reflect the severity of brain injury as evaluated by clinical and structural parameters. These results support the idea that ficolin-3-mediated functional LCP activity may be targeted to control injury progression in SAH.
评估作为凝集素补体途径（LCP）主要启动子的 ficolin-3 在蛛网膜下腔出血（SAH）病理和结局中的作用。
在这项初步探索性研究中，前瞻性队列研究了 39 例 SAH 患者和 20 例健康对照者的血浆 ficolin-3 浓度及其介导的功能性 LCP 活性，以及其他 LCP 启动子（甘露糖结合凝集素、ficolin-2 和 ficolin-1）、C3 活化产物和可溶性 C5b-9 末端复合物的浓度。记录的参数包括：使用世界神经外科学会分级量表评估的 SAH 严重程度；血管痉挛，定义为血管狭窄的血管造影证实的神经恶化；脑缺血，定义为出院前 CT 扫描显示的低密病灶；6 个月结局，使用格拉斯哥预后量表评估。
与对照组相比，患者的 ficolin-3 无变化。然而，值得注意的是，ficolin-3 介导的功能性 LCP 活性降低。血浆 ficolin-3 和 ficolin-3 介导的功能性 LCP 活性水平较低与 SAH 严重程度、血管痉挛和脑缺血有关。此外，功能不良结局患者的 ficolin-3 功能性 LCP 活性降低。
我们的数据提供了证据，表明 LCP 在 SAH 后被激活，并且实际的血浆 ficolin-3 浓度反映了通过临床和结构参数评估的脑损伤严重程度。这些结果支持 ficolin-3 介导的功能性 LCP 活性可能被靶向以控制 SAH 中损伤进展的观点。
