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Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke

BACKGROUND: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke. METHODS: Pla...

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Autores principales: Zangari, R., Zanier, E. R., Torgano, G., Bersano, A., Beretta, S., Beghi, E., Casolla, B., Checcarelli, N., Lanfranconi, S., Maino, A., Mandelli, C., Micieli, G., Orzi, F., Picetti, E., Silvestrini, M., Stocchetti, N., Zecca, B., Garred, P., De Simoni, M. G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721111/
https://www.ncbi.nlm.nih.gov/pubmed/26792363
http://dx.doi.org/10.1186/s12974-016-0481-2
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author Zangari, R.
Zanier, E. R.
Torgano, G.
Bersano, A.
Beretta, S.
Beghi, E.
Casolla, B.
Checcarelli, N.
Lanfranconi, S.
Maino, A.
Mandelli, C.
Micieli, G.
Orzi, F.
Picetti, E.
Silvestrini, M.
Stocchetti, N.
Zecca, B.
Garred, P.
De Simoni, M. G.
author_facet Zangari, R.
Zanier, E. R.
Torgano, G.
Bersano, A.
Beretta, S.
Beghi, E.
Casolla, B.
Checcarelli, N.
Lanfranconi, S.
Maino, A.
Mandelli, C.
Micieli, G.
Orzi, F.
Picetti, E.
Silvestrini, M.
Stocchetti, N.
Zecca, B.
Garred, P.
De Simoni, M. G.
author_sort Zangari, R.
collection PubMed
description BACKGROUND: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke. METHODS: Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS). RESULTS: Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 μg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 μg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 μg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 μg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11–4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90–0.99, p = 0.0001). CONCLUSIONS: The ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0481-2) contains supplementary material, which is available to authorized users.
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spelling pubmed-47211112016-01-22 Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke Zangari, R. Zanier, E. R. Torgano, G. Bersano, A. Beretta, S. Beghi, E. Casolla, B. Checcarelli, N. Lanfranconi, S. Maino, A. Mandelli, C. Micieli, G. Orzi, F. Picetti, E. Silvestrini, M. Stocchetti, N. Zecca, B. Garred, P. De Simoni, M. G. J Neuroinflammation Research BACKGROUND: Several lines of evidence support the involvement of the lectin pathway of complement (LP) in the pathogenesis of acute ischemic stroke. The aim of this multicenter observational study was to assess the prognostic value of different circulating LP initiators in acute stroke. METHODS: Plasma levels of the LP initiators ficolin-1, -2, and -3 and mannose-binding lectin (MBL) were measured in 80 stroke patients at 6 h only and in 85 patients at 48 h and later. Sixty-one age- and sex-matched healthy individuals served as controls. Stroke severity was measured on admission using the National Institutes of Health Stroke Scale (NIHSS). The outcome was measured at 90 days by the modified Rankin Scale (mRS). RESULTS: Ficolin-1 was decreased in patients compared with controls measured at 6 h (median 0.13 vs 0.33 μg/ml, respectively, p < 0.0001). At 48 h, ficolin-1 was significantly higher (0.45 μg/ml, p < 0.0001) compared to the 6 h samples and to controls. Likewise, ficolin-2 was decreased at 6 h (2.70 vs 4.40 μg/ml, p < 0.0001) but not at 48 h. Ficolin-3 was decreased both at 6 and 48 h (17.3 and 18.23 vs 21.5 μg/ml, p < 0.001 and <0.05, respectively). For MBL no difference was detected between patients and controls or within patients at the different time points. In multivariate analysis, early ficolin-1 was independently associated with unfavorable mRS outcome (adjusted odds ratio (OR): 2.21, confidence interval (CI) 95 % 1.11–4.39, p = 0.023). Early ficolin-1 improved the discriminating ability of an outcome model including NIHSS and age (area under the curve (AUC) 0.95, CI 95 % 0.90–0.99, p = 0.0001). CONCLUSIONS: The ficolins are consumed within 6 h after stroke implicating activation of the LP. Early ficolin-1 is selectively related to 3-month unfavorable outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12974-016-0481-2) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-20 /pmc/articles/PMC4721111/ /pubmed/26792363 http://dx.doi.org/10.1186/s12974-016-0481-2 Text en © Zangari et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zangari, R.
Zanier, E. R.
Torgano, G.
Bersano, A.
Beretta, S.
Beghi, E.
Casolla, B.
Checcarelli, N.
Lanfranconi, S.
Maino, A.
Mandelli, C.
Micieli, G.
Orzi, F.
Picetti, E.
Silvestrini, M.
Stocchetti, N.
Zecca, B.
Garred, P.
De Simoni, M. G.
Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke
title Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke
title_full Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke
title_fullStr Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke
title_full_unstemmed Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke
title_short Early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke
title_sort early ficolin-1 is a sensitive prognostic marker for functional outcome in ischemic stroke
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4721111/
https://www.ncbi.nlm.nih.gov/pubmed/26792363
http://dx.doi.org/10.1186/s12974-016-0481-2
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