title: Affinity proteomic profiling of plasma, cerebrospinal fluid, and brain tissue within multiple sclerosis.
abstract: The brain is a vital organ and because it is well shielded from the outside environment, possibilities for noninvasive analysis are often limited. Instead, fluids taken from the spinal cord or circulatory system are preferred sources for the discovery of candidate markers within neurological diseases. In the context of multiple sclerosis (MS), we applied an affinity proteomic strategy and screened 22 plasma samples with 4595 antibodies (3450 genes) on bead arrays, then defined 375 antibodies (334 genes) for targeted analysis in a set of 172 samples and finally used 101 antibodies (43 genes) on 443 plasma as well as 573 cerebrospinal spinal fluid (CSF) samples. This revealed alteration of protein profiles in relation to MS subtypes for IRF8, IL7, METTL14, SLC30A7, and GAP43. Respective antibodies were subsequently used for immunofluorescence on human post-mortem brain tissue with MS pathology for expression and association analysis. There, antibodies for IRF8, IL7, and METTL14 stained neurons in proximity of lesions, which highlighted these candidate protein targets for further studies within MS and brain tissue. The affinity proteomic translation of profiles discovered by profiling human body fluids and tissue provides a powerful strategy to suggest additional candidates to studies of neurological disorders.
authors.affiliation: Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology , Stockholm 171 21, Sweden.
authors.forename: Sanna
authors.initials: S
authors.lastname: Byström
authors.forename: Burcu
authors.initials: B
authors.lastname: Ayoglu
authors.forename: Anna
authors.initials: A
authors.lastname: Häggmark
authors.forename: Nicholas
authors.initials: N
authors.lastname: Mitsios
authors.forename: Mun-Gwan
authors.initials: MG
authors.lastname: Hong
authors.forename: Kimi
authors.initials: K
authors.lastname: Drobin
authors.forename: Björn
authors.initials: B
authors.lastname: Forsström
authors.forename: Claudia
authors.initials: C
authors.lastname: Fredolini
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.forename: Sandra
authors.initials: S
authors.lastname: Amor
authors.forename: Mathias
authors.initials: M
authors.lastname: Uhlén
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Jan
authors.initials: J
authors.lastname: Mulder
authors.forename: Peter
authors.initials: P
authors.lastname: Nilsson
authors.forename: Jochen M
authors.initials: JM
authors.lastname: Schwenk
mesh_terms: D000906:Antibodies; D001921:Brain / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D009103:Multiple Sclerosis / Q000097:blood* / Q000378:metabolism*; D009426:Netherlands; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*
chemical_list: D000906:Antibodies; D020543:Proteome
keywords: CSF; antibodies; brain tissue; immunofluorescence; multiple sclerosis; plasma; suspension bead arrays