title: Distinction and temporal stability of conformational epitopes on myelin oligodendrocyte glycoprotein recognized by patients with different inflammatory central nervous system diseases.
abstract: Autoantibodies targeting conformationally intact myelin oligodendrocyte glycoprotein (MOG) are found in different inflammatory diseases of the CNS, but their antigenic epitopes have not been mapped. We expressed mutants of MOG on human HeLa cells and analyzed sera from 111 patients (104 children, 7 adults) who recognized cell-bound human MOG, but had different diseases, including acute disseminated encephalomyelitis (ADEM), one episode of transverse myelitis or optic neuritis, multiple sclerosis (MS), anti-aquaporin-4 (AQP4)-negative neuromyelitis optica (NMO), and chronic relapsing inflammatory optic neuritis (CRION). We obtained insight into the recognition of epitopes in 98 patients. All epitopes identified were located at loops connecting the β strands of MOG. The most frequently recognized MOG epitope was revealed by the P42S mutation positioned in the CC'-loop. Overall, we distinguished seven epitope patterns, including the one mainly recognized by mouse mAbs. In half of the patients, the anti-MOG response was directed to a single epitope. The epitope specificity was not linked to certain disease entities. Longitudinal analysis of 11 patients for up to 5 y indicated constant epitope recognition without evidence for intramolecular epitope spreading. Patients who rapidly lost their anti-MOG IgG still generated a long-lasting IgG response to vaccines, indicating that their loss of anti-MOG reactivity did not reflect a general lack of capacity for long-standing IgG responses. The majority of human anti-MOG Abs did not recognize rodent MOG, which has implications for animal studies. Our findings might assist in future detection of potential mimotopes and pave the way to Ag-specific depletion.
authors.affiliation: Institute of Clinical Neuroimmunology, Ludwig-Maximilians-University, 81377 Munich, Germany;
authors.forename: Marie C
authors.initials: MC
authors.lastname: Mayer
authors.forename: Constanze
authors.initials: C
authors.lastname: Breithaupt
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schanda
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostásy
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brilot
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
authors.forename: Dieter
authors.initials: D
authors.lastname: Jenne
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Pröbstel
authors.forename: Klaus
authors.initials: K
authors.lastname: Dornmair
authors.forename: Hartmut
authors.initials: H
authors.lastname: Wekerle
authors.forename: Reinhard
authors.initials: R
authors.lastname: Hohlfeld
authors.forename: Brenda
authors.initials: B
authors.lastname: Banwell
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
authors.forename: Edgar
authors.initials: E
authors.lastname: Meinl
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000235:genetics / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D055550:Protein Stability; D016415:Sequence Alignment; D014162:Transfection; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D007074:Immunoglobulin G; D063308:Myelin-Oligodendrocyte Glycoprotein