Ficolin-3-mediated lectin complement pathway activation in patients with subarachnoid hemorrhage

Neurology. 2014 Jan 14;82(2):126-34. doi: 10.1212/WNL.0000000000000020. Epub 2013 Dec 11.

Abstract

Objectives: To assess the involvement of ficolin-3, the main initiator of the lectin complement pathway (LCP), in subarachnoid hemorrhage (SAH) pathology and outcome.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Brain Ischemia / etiology
  • Brain Ischemia / physiopathology
  • Brain Ischemia / surgery
  • Cohort Studies
  • Complement Pathway, Mannose-Binding Lectin / drug effects
  • Complement Pathway, Mannose-Binding Lectin / physiology*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Ficolins
  • Glycoproteins / physiology*
  • Humans
  • Lectins / pharmacology
  • Lectins / physiology*
  • Male
  • Middle Aged
  • Neurosurgical Procedures
  • Prospective Studies
  • Subarachnoid Hemorrhage / blood*
  • Subarachnoid Hemorrhage / pathology
  • Subarachnoid Hemorrhage / surgery
  • Tomography, X-Ray Computed
  • Treatment Outcome
  • Vasospasm, Intracranial / etiology
  • Vasospasm, Intracranial / physiopathology
  • Vasospasm, Intracranial / surgery

Substances

  • FCN3 protein, human
  • Glycoproteins
  • Lectins