Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke

<p>Abstract</p> <p>Background</p> <p>A number of data indicate that the lectin pathway of complement activation contributes to the pathophysiology of ischemic stroke. The lectin pathway may be triggered by the binding of mannose-binding lectin (MBL), ficolin-2 or ficoli...

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Main Authors: Füst George, Munthe-Fog Lea, Illes Zsolt, Széplaki Gábor, Molnar Tihamér, Pusch Gabriella, Hirschberg Kristóf, Szegedi Robert, Széplaki Zoltán, Prohászka Zoltán, Skjoedt Mikkel-Ole, Garred Peter
Format: Article
Language:English
Published: BMC 2011-12-01
Series:Journal of Neuroinflammation
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Online Access:http://www.jneuroinflammation.com/content/8/1/185
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author Füst George
Munthe-Fog Lea
Illes Zsolt
Széplaki Gábor
Molnar Tihamér
Pusch Gabriella
Hirschberg Kristóf
Szegedi Robert
Széplaki Zoltán
Prohászka Zoltán
Skjoedt Mikkel-Ole
Garred Peter
author_facet Füst George
Munthe-Fog Lea
Illes Zsolt
Széplaki Gábor
Molnar Tihamér
Pusch Gabriella
Hirschberg Kristóf
Szegedi Robert
Széplaki Zoltán
Prohászka Zoltán
Skjoedt Mikkel-Ole
Garred Peter
author_sort Füst George
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>A number of data indicate that the lectin pathway of complement activation contributes to the pathophysiology of ischemic stroke. The lectin pathway may be triggered by the binding of mannose-binding lectin (MBL), ficolin-2 or ficolin-3 to different ligands. Although several papers demonstrated the significance of MBL in ischemic stroke, the role of ficolins has not been examined.</p> <p>Methods</p> <p>Sera were obtained within 12 hours after the onset of ischemic stroke (admission samples) and 3-4 days later (follow-up samples) from 65 patients. The control group comprised 100 healthy individuals and 135 patients with significant carotid stenosis (patient controls). The concentrations of ficolin-2 and ficolin-3, initiator molecules of the lectin complement pathway, were measured by ELISA methods. Concentration of C-reactive protein (CRP) was also determined by a particle-enhanced immunturbidimetric assay.</p> <p>Results</p> <p>Concentrations of both ficolin-2 and ficolin-3 were significantly (p < 0.001) decreased in both the admission and in the follow-up samples of patients with definite ischemic stroke as compared to healthy subjects. Concentrations of ficolin-2 and ficolin-3 were even higher in patient controls than in healthy subjects, indicating that the decreased levels in sera during the acute phase of stroke are related to the acute ischemic event. Ficolin-3 levels in the follow-up samples inversely correlated with the severity of stroke indicated by NIH scale on admission. In follow-up samples an inverse correlation was observed between ficolin-3 levels and concentration of S100β, an indicator of the size of cerebral infarct. Patients with low ficolin-3 levels and high CRP levels in the follow up samples had a significantly worse outcome (adjusted ORs 5.6 and 3.9, respectively) as measured by the modified Rankin scale compared to patients with higher ficolin-3 and lower CRP concentrations. High CRP concentrations were similarly predictive for worse outcome, and the effects of low ficolin-3 and high CRP were independent.</p> <p>Conclusions</p> <p>Our findings indicate that ficolin-mediated lectin pathways of complement activation contribute to the pathogenesis of ischemic stroke and may be additive to complement-independent inflammatory processes.</p>
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spelling doaj.art-2c171fec0ebf46b887290287deace6402022-12-22T01:24:49ZengBMCJournal of Neuroinflammation1742-20942011-12-018118510.1186/1742-2094-8-185Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic strokeFüst GeorgeMunthe-Fog LeaIlles ZsoltSzéplaki GáborMolnar TihamérPusch GabriellaHirschberg KristófSzegedi RobertSzéplaki ZoltánProhászka ZoltánSkjoedt Mikkel-OleGarred Peter<p>Abstract</p> <p>Background</p> <p>A number of data indicate that the lectin pathway of complement activation contributes to the pathophysiology of ischemic stroke. The lectin pathway may be triggered by the binding of mannose-binding lectin (MBL), ficolin-2 or ficolin-3 to different ligands. Although several papers demonstrated the significance of MBL in ischemic stroke, the role of ficolins has not been examined.</p> <p>Methods</p> <p>Sera were obtained within 12 hours after the onset of ischemic stroke (admission samples) and 3-4 days later (follow-up samples) from 65 patients. The control group comprised 100 healthy individuals and 135 patients with significant carotid stenosis (patient controls). The concentrations of ficolin-2 and ficolin-3, initiator molecules of the lectin complement pathway, were measured by ELISA methods. Concentration of C-reactive protein (CRP) was also determined by a particle-enhanced immunturbidimetric assay.</p> <p>Results</p> <p>Concentrations of both ficolin-2 and ficolin-3 were significantly (p < 0.001) decreased in both the admission and in the follow-up samples of patients with definite ischemic stroke as compared to healthy subjects. Concentrations of ficolin-2 and ficolin-3 were even higher in patient controls than in healthy subjects, indicating that the decreased levels in sera during the acute phase of stroke are related to the acute ischemic event. Ficolin-3 levels in the follow-up samples inversely correlated with the severity of stroke indicated by NIH scale on admission. In follow-up samples an inverse correlation was observed between ficolin-3 levels and concentration of S100β, an indicator of the size of cerebral infarct. Patients with low ficolin-3 levels and high CRP levels in the follow up samples had a significantly worse outcome (adjusted ORs 5.6 and 3.9, respectively) as measured by the modified Rankin scale compared to patients with higher ficolin-3 and lower CRP concentrations. High CRP concentrations were similarly predictive for worse outcome, and the effects of low ficolin-3 and high CRP were independent.</p> <p>Conclusions</p> <p>Our findings indicate that ficolin-mediated lectin pathways of complement activation contribute to the pathogenesis of ischemic stroke and may be additive to complement-independent inflammatory processes.</p>http://www.jneuroinflammation.com/content/8/1/185strokeischemic strokeoutcomecomplementlectin pathwayficolinsficolin-2ficolin-3CRP
spellingShingle Füst George
Munthe-Fog Lea
Illes Zsolt
Széplaki Gábor
Molnar Tihamér
Pusch Gabriella
Hirschberg Kristóf
Szegedi Robert
Széplaki Zoltán
Prohászka Zoltán
Skjoedt Mikkel-Ole
Garred Peter
Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke
Journal of Neuroinflammation
stroke
ischemic stroke
outcome
complement
lectin pathway
ficolins
ficolin-2
ficolin-3
CRP
title Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke
title_full Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke
title_fullStr Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke
title_full_unstemmed Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke
title_short Low ficolin-3 levels in early follow-up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke
title_sort low ficolin 3 levels in early follow up serum samples are associated with the severity and unfavorable outcome of acute ischemic stroke
topic stroke
ischemic stroke
outcome
complement
lectin pathway
ficolins
ficolin-2
ficolin-3
CRP
url http://www.jneuroinflammation.com/content/8/1/185
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