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

Elisa R Zanier; Rosalia Zangari; Lea Munthe-Fog; Estrid Hein; Tommaso Zoerle; Valeria Conte; Franca Orsini; Mauro Tettamanti; Nino Stocchetti; Peter Garred; Maria-Grazia De Simoni

doi:10.1212/wnl.0000000000000020

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

Elisa R Zanier, Rosalia Zangari, Lea Munthe-Fog, Estrid Hein, Tommaso Zoerle, Valeria Conte, Franca Orsini, Mauro Tettamanti, Nino Stocchetti, Peter Garred, Maria-Grazia De Simoni

Department of Clinical Medicine

23 Citations (Scopus)

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.

Original language	English
Journal	Neurology
Volume	82
Issue number	2
Pages (from-to)	126-134
Number of pages	9
ISSN	0028-3878
DOIs	https://doi.org/10.1212/wnl.0000000000000020
Publication status	Published - 14 Jan 2014

Keywords

Aged
Brain Ischemia
Cohort Studies
Complement Pathway, Mannose-Binding Lectin
Enzyme-Linked Immunosorbent Assay
Female
Glycoproteins
Humans
Lectins
Male
Middle Aged
Neurosurgical Procedures
Prospective Studies
Subarachnoid Hemorrhage
Tomography, X-Ray Computed
Treatment Outcome
Vasospasm, Intracranial

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@article{040a724a75c048718e8810bff9a7b595,

title = "Ficolin-3-mediated lectin complement pathway activation in patients with subarachnoid hemorrhage",

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.",

keywords = "Aged, Brain Ischemia, Cohort Studies, Complement Pathway, Mannose-Binding Lectin, Enzyme-Linked Immunosorbent Assay, Female, Glycoproteins, Humans, Lectins, Male, Middle Aged, Neurosurgical Procedures, Prospective Studies, Subarachnoid Hemorrhage, Tomography, X-Ray Computed, Treatment Outcome, Vasospasm, Intracranial",

author = "Zanier, {Elisa R} and Rosalia Zangari and Lea Munthe-Fog and Estrid Hein and Tommaso Zoerle and Valeria Conte and Franca Orsini and Mauro Tettamanti and Nino Stocchetti and Peter Garred and {De Simoni}, Maria-Grazia",

year = "2014",

month = jan,

day = "14",

doi = "10.1212/wnl.0000000000000020",

language = "English",

volume = "82",

pages = "126--134",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams & Wilkins",

number = "2",

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TY - JOUR

T1 - Ficolin-3-mediated lectin complement pathway activation in patients with subarachnoid hemorrhage

AU - Zanier, Elisa R

AU - Zangari, Rosalia

AU - Munthe-Fog, Lea

AU - Hein, Estrid

AU - Zoerle, Tommaso

AU - Conte, Valeria

AU - Orsini, Franca

AU - Tettamanti, Mauro

AU - Stocchetti, Nino

AU - Garred, Peter

AU - De Simoni, Maria-Grazia

PY - 2014/1/14

Y1 - 2014/1/14

N2 - 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.

AB - 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.

KW - Aged

KW - Brain Ischemia

KW - Cohort Studies

KW - Complement Pathway, Mannose-Binding Lectin

KW - Enzyme-Linked Immunosorbent Assay

KW - Female

KW - Glycoproteins

KW - Humans

KW - Lectins

KW - Male

KW - Middle Aged

KW - Neurosurgical Procedures

KW - Prospective Studies

KW - Subarachnoid Hemorrhage

KW - Tomography, X-Ray Computed

KW - Treatment Outcome

KW - Vasospasm, Intracranial

U2 - 10.1212/wnl.0000000000000020

DO - 10.1212/wnl.0000000000000020

M3 - Journal article

C2 - 24336142

SN - 0028-3878

VL - 82

SP - 126

EP - 134

JO - Neurology

JF - Neurology

IS - 2

ER -

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

Abstract

Keywords

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