title: Localisation of citrullinated proteins in normal appearing white matter and lesions in the central nervous system in multiple sclerosis.
abstract: Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease, considered to be autoimmune in origin. Post-translational modification of central nervous system proteins, including glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP), through citrullination of arginine residues, may lead to exposure of neoepitopes, triggering autoimmunity. Here we investigated the expression of citrullinated proteins in active MS lesions, MS normal appearing white matter and control brain white matter. We demonstrate increased citrullinated GFAP and MBP by immunohistochemistry and western blotting in areas of ongoing demyelination, suggesting a pivotal role for deimination of GFAP and MBP in MS pathogenesis MS.
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, S1 1WB South Yorkshire, UK.
authors.forename: Claire M
authors.initials: CM
authors.lastname: Bradford
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, S1 1WB South Yorkshire, UK.
authors.forename: Inês
authors.initials: I
authors.lastname: Ramos
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, S1 1WB South Yorkshire, UK.
authors.forename: Alison K
authors.initials: AK
authors.lastname: Cross
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, S1 1WB South Yorkshire, UK.
authors.forename: Gail
authors.initials: G
authors.lastname: Haddock
authors.affiliation: Neuropathology Laboratory, Department of Pathology, Royal Group of Hospitals Trust, Grosvenor Road, Belfast, Northern Ireland BT12 6BL, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: McQuaid
authors.affiliation: Department of Neurology, University of Alabama at Birmingham and Birmingham Veterans Administration Medical Centre, Birmingham, AL 35249-7340, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Nicholas
authors.affiliation: Biomedical Research Centre, Sheffield Hallam University, Howard Street, S1 1WB South Yorkshire, UK. Electronic address: n.woodroofe@shu.ac.uk.
authors.forename: M Nicola
authors.initials: MN
authors.lastname: Woodroofe
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000378:metabolism; D001253:Astrocytes / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D004676:Myelin Basic Protein / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D000076342:Protein-Arginine Deiminases
chemical_list: D005904:Glial Fibrillary Acidic Protein; D006684:HLA-DR Antigens; C571326:MOG protein, human; D004676:Myelin Basic Protein; D063308:Myelin-Oligodendrocyte Glycoprotein; D001120:Arginine; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases
keywords: Autoimmunity; Citrullination; Glial fibrillary acidic protein; Multiple sclerosis; Myelin basic protein