Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis
Abstract Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hi...
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Nature Portfolio
2021
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oai:doaj.org-article:c8d8de9b2ad049d78f80443f46656cae2021-12-02T10:54:30ZCerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis10.1038/s41598-021-82388-w2045-2322https://doaj.org/article/c8d8de9b2ad049d78f80443f46656cae2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82388-whttps://doaj.org/toc/2045-2322Abstract Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease.Ellen F. MoslethChristian Alexander VedelerKristian Hovde LilandAnette McLeodGerd Haga BringelandLiesbeth KroondijkFrode Steingrimsen BervenArtem LysenkoChristopher J. RawlingsKarim El-Hajj EidJill Anette OpsahlBjørn Tore GjertsenKjell-Morten MyhrSonia GavassoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021) |
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Medicine R Science Q Ellen F. Mosleth Christian Alexander Vedeler Kristian Hovde Liland Anette McLeod Gerd Haga Bringeland Liesbeth Kroondijk Frode Steingrimsen Berven Artem Lysenko Christopher J. Rawlings Karim El-Hajj Eid Jill Anette Opsahl Bjørn Tore Gjertsen Kjell-Morten Myhr Sonia Gavasso Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis |
| description |
Abstract Despite intensive research, the aetiology of multiple sclerosis (MS) remains unknown. Cerebrospinal fluid proteomics has the potential to reveal mechanisms of MS pathogenesis, but analyses must account for disease heterogeneity. We previously reported explorative multivariate analysis by hierarchical clustering of proteomics data of MS patients and controls, which resulted in two groups of individuals. Grouping reflected increased levels of intrathecal inflammatory response proteins and decreased levels of proteins involved in neural development in one group relative to the other group. MS patients and controls were present in both groups. Here we reanalysed these data and we also reanalysed data from an independent cohort of patients diagnosed with clinically isolated syndrome (CIS), who have symptoms of MS without evidence of dissemination in space and/or time. Some, but not all, CIS patients had intrathecal inflammation. The analyses reported here identified a common protein signature of MS/CIS that was not linked to elevated intrathecal inflammation. The signature included low levels of complement proteins, semaphorin-7A, reelin, neural cell adhesion molecules, inter-alpha-trypsin inhibitor heavy chain H2, transforming growth factor beta 1, follistatin-related protein 1, malate dehydrogenase 1 cytoplasmic, plasma retinol-binding protein, biotinidase, and transferrin, all known to play roles in neural development. Low levels of these proteins suggest that MS/CIS patients suffer from abnormally low oxidative capacity that results in disrupted neural development from an early stage of the disease. |
| format |
article |
| author |
Ellen F. Mosleth Christian Alexander Vedeler Kristian Hovde Liland Anette McLeod Gerd Haga Bringeland Liesbeth Kroondijk Frode Steingrimsen Berven Artem Lysenko Christopher J. Rawlings Karim El-Hajj Eid Jill Anette Opsahl Bjørn Tore Gjertsen Kjell-Morten Myhr Sonia Gavasso |
| author_facet |
Ellen F. Mosleth Christian Alexander Vedeler Kristian Hovde Liland Anette McLeod Gerd Haga Bringeland Liesbeth Kroondijk Frode Steingrimsen Berven Artem Lysenko Christopher J. Rawlings Karim El-Hajj Eid Jill Anette Opsahl Bjørn Tore Gjertsen Kjell-Morten Myhr Sonia Gavasso |
| author_sort |
Ellen F. Mosleth |
| title |
Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis |
| title_short |
Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis |
| title_full |
Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis |
| title_fullStr |
Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis |
| title_full_unstemmed |
Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis |
| title_sort |
cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/c8d8de9b2ad049d78f80443f46656cae |
| work_keys_str_mv |
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1718396493712326656 |