title: Antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in a model of central nervous system autoimmune inflammatory disease.
abstract: Neurodegeneration is believed to be the primary cause of permanent, long-term disability in patients with multiple sclerosis. The cause of neurodegeneration in multiple sclerosis appears to be multifactorial. One mechanism that has been implicated in the pathogenesis of neurodegeneration in multiple sclerosis is the targeting of neuronal and axonal antigens by autoantibodies. Multiple sclerosis patients develop antibodies to the RNA-binding protein, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which is enriched in neurons. We hypothesized that anti-hnRNP A1 antibodies would contribute to neurodegeneration in an animal model of multiple sclerosis.
  
  
  
  Following induction of experimental autoimmune encephalomyelitis (EAE) by direct immunization with myelin oligodendrocyte glycoprotein, mice were injected with anti-hnRNP A1 or control antibodies. Animals were examined clinically, and the central nervous system (CNS) tissues were tested for neurodegeneration with Fluoro-Jade C, a marker of degenerating neural elements.
  
  
  
  Injection of anti-hnRNP A1 antibodies in mice with EAE worsened clinical disease, altered the clinical disease phenotype, and caused neurodegeneration preferentially in the ventral spinocerebellar tract and deep white matter of the cerebellum in the CNS. Neurodegeneration in mice injected with hnRNP A1-M9 antibodies compared to control groups was consistent with "dying back" axonal degeneration.
  
  
  
  These data suggest that antibodies to the RNA-binding protein hnRNP A1 contribute to neurodegeneration in immune-mediated disease of the CNS.
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Room 415, Memphis, TN, 38163, USA.|The Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Douglas
authors.affiliation: Research Service, VA Medical Center, Memphis, TN, USA.|Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Room 415, Memphis, TN, 38163, USA.|The Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Lidia A
authors.initials: LA
authors.lastname: Gardner
authors.affiliation: Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Room 415, Memphis, TN, 38163, USA.|The Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Hannah E
authors.initials: HE
authors.lastname: Salapa
authors.affiliation: Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lalor
authors.affiliation: Research Service, VA Medical Center, Memphis, TN, USA.|Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Room 415, Memphis, TN, 38163, USA.|The Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Neurology, University of Michigan Medical School, Ann Arbor, MI, USA.|Neurology Service, VA Ann Arbor Health Care System, Ann Arbor, MI, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Segal
authors.affiliation: Laboratory of Neuronal Structure & Function, The Salk Institute, La Jolla, CA, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sawchenko
authors.affiliation: Research Service, VA Medical Center, Memphis, TN, USA. mlevin@uthsc.edu.|Department of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Room 415, Memphis, TN, 38163, USA. mlevin@uthsc.edu.|The Neuroscience Institute, University of Tennessee Health Science Center, Memphis, TN, USA. mlevin@uthsc.edu.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Levin
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D019636:Neurodegenerative Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*
chemical_list: D001323:Autoantibodies; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; C000619657:Hnrnpa1 protein, mouse
keywords: Experimental autoimmune encephalomyelitis; Multiple sclerosis; Neurodegeneration; RNA-binding protein; hnRNP A1