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Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis
Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genome-wide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholi...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383591/ https://www.ncbi.nlm.nih.gov/pubmed/25835709 http://dx.doi.org/10.1371/journal.pone.0122048 |
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author | Aeinehband, Shahin Lindblom, Rickard P. F. Al Nimer, Faiez Vijayaraghavan, Swetha Sandholm, Kerstin Khademi, Mohsen Olsson, Tomas Nilsson, Bo Ekdahl, Kristina Nilsson Darreh-Shori, Taher Piehl, Fredrik |
author_facet | Aeinehband, Shahin Lindblom, Rickard P. F. Al Nimer, Faiez Vijayaraghavan, Swetha Sandholm, Kerstin Khademi, Mohsen Olsson, Tomas Nilsson, Bo Ekdahl, Kristina Nilsson Darreh-Shori, Taher Piehl, Fredrik |
author_sort | Aeinehband, Shahin |
collection | PubMed |
description | Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genome-wide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with ≥9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone. |
format | Online Article Text |
id | pubmed-4383591 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-43835912015-04-09 Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis Aeinehband, Shahin Lindblom, Rickard P. F. Al Nimer, Faiez Vijayaraghavan, Swetha Sandholm, Kerstin Khademi, Mohsen Olsson, Tomas Nilsson, Bo Ekdahl, Kristina Nilsson Darreh-Shori, Taher Piehl, Fredrik PLoS One Research Article Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genome-wide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with ≥9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone. Public Library of Science 2015-04-02 /pmc/articles/PMC4383591/ /pubmed/25835709 http://dx.doi.org/10.1371/journal.pone.0122048 Text en © 2015 Aeinehband et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Aeinehband, Shahin Lindblom, Rickard P. F. Al Nimer, Faiez Vijayaraghavan, Swetha Sandholm, Kerstin Khademi, Mohsen Olsson, Tomas Nilsson, Bo Ekdahl, Kristina Nilsson Darreh-Shori, Taher Piehl, Fredrik Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis |
title | Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis |
title_full | Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis |
title_fullStr | Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis |
title_full_unstemmed | Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis |
title_short | Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis |
title_sort | complement component c3 and butyrylcholinesterase activity are associated with neurodegeneration and clinical disability in multiple sclerosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383591/ https://www.ncbi.nlm.nih.gov/pubmed/25835709 http://dx.doi.org/10.1371/journal.pone.0122048 |
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