title: Ficolin-3-mediated lectin complement pathway activation in patients with subarachnoid hemorrhage.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: 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.
authors: Elisa R
authors: ER
authors: Zanier
authors: Rosalia
authors: R
authors: Zangari
authors: Lea
authors: L
authors: Munthe-Fog
authors: Estrid
authors: E
authors: Hein
authors: Tommaso
authors: T
authors: Zoerle
authors: Valeria
authors: V
authors: Conte
authors: Franca
authors: F
authors: Orsini
authors: Mauro
authors: M
authors: Tettamanti
authors: Nino
authors: N
authors: Stocchetti
authors: Peter
authors: P
authors: Garred
authors: Maria-Grazia
authors: MG
authors: De Simoni
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology / Q000601:surgery; D015331:Cohort Studies; D037582:Complement Pathway, Mannose-Binding Lectin / Q000187:drug effects / Q000502:physiology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D037102:Lectins / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019635:Neurosurgical Procedures; D011446:Prospective Studies; D013345:Subarachnoid Hemorrhage / Q000097:blood* / Q000473:pathology / Q000601:surgery; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D020301:Vasospasm, Intracranial / Q000209:etiology / Q000503:physiopathology / Q000601:surgery; D000097604:Ficolins
chemical_list: D006023:Glycoproteins; D037102:Lectins; D000097604:Ficolins; C109662:FCN3 protein, human