title: Neurofascin 186 specific autoantibodies induce axonal injury and exacerbate disease severity in experimental autoimmune encephalomyelitis.
abstract: Axonal injury is considered the major cause of chronic disability in multiple sclerosis (MS) patients, however the mechanisms behind remain still unclear. Recently, it was demonstrated that autoantibodies against Neurofascin, a cell adhesion molecule within the adult nervous system, can contribute to the development of axonal pathology in some patients. We compared the ability of the two different isoforms of Neurofascin, Nfasc155 and Nfasc186, to induce a pathogenic antibody response in the Dark Agouti (DA) rat. Animals were immunized with recombinant proteins prior to induction of experimental autoimmune encephalomyelitis (EAE) by adoptive transfer of activated MOG-specific T cells. Only Nfasc186 induced an axopathic autoantibody response in vivo, despite extensive cross reactivity between the two isoforms as shown by ELISA and flow cytometry. In this case, using transfected cell lines failed to differentiate between pathogenic and non-pathogenic responses. These findings have important implications with respect to the usage of cell based assays as an approach to detect pathologically relevant autoantibodies in clinical samples.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK. maren.lindner@glasgow.ac.uk
authors.forename: Maren
authors.initials: M
authors.lastname: Lindner
authors.forename: Judy King Man
authors.initials: JK
authors.lastname: Ng
authors.forename: Sonja
authors.initials: S
authors.lastname: Hochmeister
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
authors.forename: Christopher
authors.initials: C
authors.lastname: Linington
mesh_terms: D019264:Adoptive Transfer / Q000009:adverse effects; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism*; D001369:Axons / Q000276:immunology / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000009:adverse effects / Q000276:immunology*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008213:Lymphocyte Activation; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000009:adverse effects; D009414:Nerve Growth Factors / Q000009:adverse effects / Q000276:immunology*; D020033:Protein Isoforms / Q000276:immunology; D051381:Rats; D018709:Statistics, Nonparametric
chemical_list: D001323:Autoantibodies; D015815:Cell Adhesion Molecules; D063308:Myelin-Oligodendrocyte Glycoprotein; D009414:Nerve Growth Factors; C504594:Nfasc protein, rat; D020033:Protein Isoforms
keywords: EAE; Multiple sclerosis; Neurofascin; Pathogenic antibody