title: Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis.
abstract: BACKGROUND
  Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clinical relevance of these epitopes in MS.
  
  
  METHODS
  Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to 3 different MOG isoforms, and quantitative titers correlated with clinical characteristics. mAbs defined unique immunodominant epitopes distinct to each of the isoforms.
  
  
  RESULTS
  In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2% of samples high-titer anti-MOG antibodies were identified. In contrast to anti-MOG reactivity observed in a mouse model of MS, in patients with MS these never reacted with ubiquitously exposed epitopes. Moreover, in patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r = 0.574; p = 0.025).
  
  
  CONCLUSIONS
  Thus high-titer reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS. Our study provides valuable information about requirements of anti-MOG reactivity for being regarded as a prognostic biomarker in a subtype of MS.
authors.affiliation: Neuroimmunology Laboratories, Department of Neurology, University of California San Francisco, CA, USA. menge@uni-duesseldorf.de
authors.forename: Til
authors.initials: T
authors.lastname: Menge
authors.forename: Patrice H
authors.initials: PH
authors.lastname: Lalive
authors.forename: H Christian
authors.initials: HC
authors.lastname: von Büdingen
authors.forename: Claude P
authors.initials: CP
authors.lastname: Genain
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000097:blood / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D051379:Mice; D009103:Multiple Sclerosis / Q000097:blood / Q000276:immunology*; D009185:Myelin Proteins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D015415:Biomarkers; D000939:Epitopes; D016056:Immunodominant Epitopes; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D020033:Protein Isoforms
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