Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis

A - Papers appearing in refereed journals

Mosleth, E. F., Vedeler, C. A., Liland, K. H., Mcleod, A., Bringeland, G. H., Kroondijk, L., Berven, F. S., Lysenko, A., Rawlings, C. J., Eid, K. E-H., Opsahl, J. A., Gjertsen, B. T., Myhr, K-M. and Gavasso, S. 2021. Cerebrospinal fluid proteome shows disrupted neuronal development in multiple sclerosis. Scientific Reports. 11, p. 4087. https://doi.org/10.1038/s41598-021-82388-w

AuthorsMosleth, E. F., Vedeler, C. A., Liland, K. H., Mcleod, A., Bringeland, G. H., Kroondijk, L., Berven, F. S., Lysenko, A., Rawlings, C. J., Eid, K. E-H., Opsahl, J. A., Gjertsen, B. T., Myhr, K-M. and Gavasso, S.
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.

Year of Publication2021
JournalScientific Reports
Journal citation11, p. 4087
Digital Object Identifier (DOI)https://doi.org/10.1038/s41598-021-82388-w
Open accessPublished as ‘gold’ (paid) open access
FunderBiotechnology and Biological Sciences Research Council
Publisher's version
Output statusPublished
Publication dates
Online18 Feb 2021
ISSN2045-2322
PublisherNature Publishing Group

Permalink - https://repository.rothamsted.ac.uk/item/98493/cerebrospinal-fluid-proteome-shows-disrupted-neuronal-development-in-multiple-sclerosis

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