eprintid: 10056834 rev_number: 20 eprint_status: archive userid: 608 dir: disk0/10/05/68/34 datestamp: 2018-09-24 08:17:28 lastmod: 2021-10-24 23:23:27 status_changed: 2018-09-24 08:17:28 type: article metadata_visibility: show creators_name: Herman, S creators_name: Khoonsari, PE creators_name: Tolf, A creators_name: Steinmetz, J creators_name: Zetterberg, H creators_name: Åkerfeldt, T creators_name: Jakobsson, P-J creators_name: Larsson, A creators_name: Spjuth, O creators_name: Burman, J creators_name: Kultima, K title: Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: D07 divisions: F86 keywords: biomarker, data integration, disease progression, metabolomics, multiple sclerosis note: This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. abstract: Molecular networks in neurological diseases are complex. Despite this fact, contemporary biomarkers are in most cases interpreted in isolation, leading to a significant loss of information and power. We present an analytical approach to scrutinize and combine information from biomarkers originating from multiple sources with the aim of discovering a condensed set of biomarkers that in combination could distinguish the progressive degenerative phenotype of multiple sclerosis (SPMS) from the relapsing-remitting phenotype (RRMS). Methods: Clinical and magnetic resonance imaging (MRI) data were integrated with data from protein and metabolite measurements of cerebrospinal fluid, and a method was developed to sift through all the variables to establish a small set of highly informative measurements. This prospective study included 16 SPMS patients, 30 RRMS patients and 10 controls. Protein concentrations were quantitated with multiplexed fluorescent bead-based immunoassays and ELISA. The metabolome was recorded using liquid chromatography-mass spectrometry. Clinical follow-up data of the SPMS patients were used to assess disease progression and development of disability. Results: Eleven variables were in combination able to distinguish SPMS from RRMS patients with high confidence superior to any single measurement. The identified variables consisted of three MRI variables: the size of the spinal cord and the third ventricle and the total number of T1 hypointense lesions; six proteins: galectin-9, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor alpha (TGF-α), tumor necrosis factor alpha (TNF-α), soluble CD40L (sCD40L) and platelet-derived growth factor AA (PDGF-AA); and two metabolites: 20β-dihydrocortisol (20β-DHF) and indolepyruvate. The proteins myelin basic protein (MBP) and macrophage-derived chemokine (MDC), as well as the metabolites 20β-DHF and 5,6-dihydroxyprostaglandin F1a (5,6-DH-PGF1), were identified as potential biomarkers of disability progression. Conclusion: Our study demonstrates, in a limited but well-defined and data-rich cohort, the importance and value of combining multiple biomarkers to aid diagnostics and track disease progression. date: 2018 date_type: published official_url: http://dx.doi.org/10.7150/thno.26249 oa_status: green full_text_type: pub pmcid: PMC6134925 language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1583021 doi: 10.7150/thno.26249 pii: thnov08p4477 lyricists_name: Zetterberg, Henrik lyricists_id: HZETT94 actors_name: Bracey, Alan actors_id: ABBRA90 actors_role: owner full_text_status: public publication: Theranostics volume: 8 number: 16 pagerange: 4477-4490 event_location: Australia issn: 1838-7640 citation: Herman, S; Khoonsari, PE; Tolf, A; Steinmetz, J; Zetterberg, H; Åkerfeldt, T; Jakobsson, P-J; ... Kultima, K; + view all <#> Herman, S; Khoonsari, PE; Tolf, A; Steinmetz, J; Zetterberg, H; Åkerfeldt, T; Jakobsson, P-J; Larsson, A; Spjuth, O; Burman, J; Kultima, K; - view fewer <#> (2018) Integration of magnetic resonance imaging and protein and metabolite CSF measurements to enable early diagnosis of secondary progressive multiple sclerosis. Theranostics , 8 (16) pp. 4477-4490. 10.7150/thno.26249 <https://doi.org/10.7150/thno.26249>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10056834/1/v08p4477.pdf