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Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study

BACKGROUND: This exploratory study investigated the time-course of lectin complement pathway (LCP) initiators in cerebrospinal fluid (CSF) and plasma in patients with subarachnoid hemorrhage (SAH), as well as their relationship to delayed cerebral ischemia (DCI) and functional outcome. METHODS: Conc...

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Autores principales: Matzen, Jeppe Sillesen, Krogh, Charlotte Loumann, Forman, Julie Lyng, Garred, Peter, Møller, Kirsten, Bache, Søren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661172/
https://www.ncbi.nlm.nih.gov/pubmed/33183322
http://dx.doi.org/10.1186/s12974-020-01979-y
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author Matzen, Jeppe Sillesen
Krogh, Charlotte Loumann
Forman, Julie Lyng
Garred, Peter
Møller, Kirsten
Bache, Søren
author_facet Matzen, Jeppe Sillesen
Krogh, Charlotte Loumann
Forman, Julie Lyng
Garred, Peter
Møller, Kirsten
Bache, Søren
author_sort Matzen, Jeppe Sillesen
collection PubMed
description BACKGROUND: This exploratory study investigated the time-course of lectin complement pathway (LCP) initiators in cerebrospinal fluid (CSF) and plasma in patients with subarachnoid hemorrhage (SAH), as well as their relationship to delayed cerebral ischemia (DCI) and functional outcome. METHODS: Concentrations of ficolin-1, ficolin-2, ficolin-3, and mannose-binding lectin (MBL) were analyzed in CSF and plasma from patients with SAH. Samples were collected daily from admission until day 9 (CSF; N_(PATIENTS) = 63, n_(SAMPLES) = 399) and day 8 (plasma; N_(PATIENTS) = 50, n_(SAMPLES) = 358), respectively. Twelve neurologically healthy patients undergoing spinal anesthesia and 12 healthy blood donors served as controls. The development of DCI during hospitalization and functional outcome at 3 months (modified Rankin Scale) were registered for patients. RESULTS: On admission, CSF levels of all LCP initiators were increased in SAH patients compared with healthy controls. Levels declined gradually over days in patients; however, a biphasic course was observed for ficolin-1. Increased CSF levels of all LCP initiators were associated with a poor functional outcome in univariate analyses. This relationship persisted for ficolin-1 and MBL in multivariate analysis after adjustments for confounders (age, sex, clinical severity, distribution and amount of blood on CT-imaging) and multiple testing (1.87 ng/mL higher in average, 95% CI, 1.17 to 2.99 and 1.69 ng/mL higher in average, 95% CI, 1.09 to 2.63, respectively). In patients who developed DCI compared with those without DCI, CSF levels of ficolin-1 and MBL tended to increase slightly more over time (p_interaction = 0.021 and 0.033, respectively); however, no association was found after adjustments for confounders and multiple testing (p-adj_interaction = 0.086 and 0.098, respectively). Plasma ficolin-1 and ficolin-3 were lower in SAH patients compared with healthy controls on all days. DCI and functional outcome were not associated with LCP initiator levels in plasma. CONCLUSION: Patients with SAH displayed elevated CSF levels of ficolin-1, ficolin-2, ficolin-3, and MBL. Increased CSF levels of ficolin-1 and MBL were associated with a poor functional outcome. TRIAL REGISTRATION: This study was a retrospective analysis of samples, which had been prospectively sampled and stored in a biobank. Registered at clinicaltrials.gov (NCT01791257, February 13, 2013, and NCT02320539, December 19, 2014). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-020-01979-y.
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spelling pubmed-76611722020-11-13 Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study Matzen, Jeppe Sillesen Krogh, Charlotte Loumann Forman, Julie Lyng Garred, Peter Møller, Kirsten Bache, Søren J Neuroinflammation Research BACKGROUND: This exploratory study investigated the time-course of lectin complement pathway (LCP) initiators in cerebrospinal fluid (CSF) and plasma in patients with subarachnoid hemorrhage (SAH), as well as their relationship to delayed cerebral ischemia (DCI) and functional outcome. METHODS: Concentrations of ficolin-1, ficolin-2, ficolin-3, and mannose-binding lectin (MBL) were analyzed in CSF and plasma from patients with SAH. Samples were collected daily from admission until day 9 (CSF; N_(PATIENTS) = 63, n_(SAMPLES) = 399) and day 8 (plasma; N_(PATIENTS) = 50, n_(SAMPLES) = 358), respectively. Twelve neurologically healthy patients undergoing spinal anesthesia and 12 healthy blood donors served as controls. The development of DCI during hospitalization and functional outcome at 3 months (modified Rankin Scale) were registered for patients. RESULTS: On admission, CSF levels of all LCP initiators were increased in SAH patients compared with healthy controls. Levels declined gradually over days in patients; however, a biphasic course was observed for ficolin-1. Increased CSF levels of all LCP initiators were associated with a poor functional outcome in univariate analyses. This relationship persisted for ficolin-1 and MBL in multivariate analysis after adjustments for confounders (age, sex, clinical severity, distribution and amount of blood on CT-imaging) and multiple testing (1.87 ng/mL higher in average, 95% CI, 1.17 to 2.99 and 1.69 ng/mL higher in average, 95% CI, 1.09 to 2.63, respectively). In patients who developed DCI compared with those without DCI, CSF levels of ficolin-1 and MBL tended to increase slightly more over time (p_interaction = 0.021 and 0.033, respectively); however, no association was found after adjustments for confounders and multiple testing (p-adj_interaction = 0.086 and 0.098, respectively). Plasma ficolin-1 and ficolin-3 were lower in SAH patients compared with healthy controls on all days. DCI and functional outcome were not associated with LCP initiator levels in plasma. CONCLUSION: Patients with SAH displayed elevated CSF levels of ficolin-1, ficolin-2, ficolin-3, and MBL. Increased CSF levels of ficolin-1 and MBL were associated with a poor functional outcome. TRIAL REGISTRATION: This study was a retrospective analysis of samples, which had been prospectively sampled and stored in a biobank. Registered at clinicaltrials.gov (NCT01791257, February 13, 2013, and NCT02320539, December 19, 2014). SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-020-01979-y. BioMed Central 2020-11-12 /pmc/articles/PMC7661172/ /pubmed/33183322 http://dx.doi.org/10.1186/s12974-020-01979-y Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. 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 in a credit line to the data.
spellingShingle Research
Matzen, Jeppe Sillesen
Krogh, Charlotte Loumann
Forman, Julie Lyng
Garred, Peter
Møller, Kirsten
Bache, Søren
Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study
title Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study
title_full Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study
title_fullStr Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study
title_full_unstemmed Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study
title_short Lectin complement pathway initiators after subarachnoid hemorrhage — an observational study
title_sort lectin complement pathway initiators after subarachnoid hemorrhage — an observational study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661172/
https://www.ncbi.nlm.nih.gov/pubmed/33183322
http://dx.doi.org/10.1186/s12974-020-01979-y
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