title: Infectious Mononucleosis Triggers Generation of IgG Auto-Antibodies against Native Myelin Oligodendrocyte Glycoprotein.
abstract: A history of infectious mononucleosis (IM), symptomatic primary infection with the Epstein Barr virus, is associated with the development of autoimmune diseases and increases the risk to develop multiple sclerosis. Here, we hypothesized that immune activation during IM triggers autoreactive immune responses. Antibody responses towards cellular antigens using a HEp-2 based indirect immunofluorescence assay and native myelin oligodendrocyte glycoprotein (MOG) using a flow cytometry-based assay were determined in 35 patients with IM and in 23 control subjects. We detected frequent immunoglobulin M (IgM) reactivity to vimentin, a major constituent of the intermediate filament family of proteins, in IM patients (27/35; 77%) but rarely in control subjects (2/23; 9%). IgG autoantibodies binding to HEp-2 cells were absent in both groups. In contrast, IgG responses to native MOG, present in up to 40% of children with inflammatory demyelinating diseases of the central nervous system (CNS), were detectable in 7/35 (20%) patients with IM but not in control subjects. Normalization of anti-vimentin IgM levels to increased total IgM concentrations during IM resulted in loss of significant differences for anti-vimentin IgM titers. Anti-MOG specific IgG responses were still detectable in a subset of three out of 35 patients with IM (9%), even after normalization to increased total IgG levels. Vimentin-specific IgM and MOG-specific IgG responses decreased following clinical resolution of acute IM symptoms. We conclude from our data that MOG-specific memory B cells are activated in subset of patients with IM.
authors.affiliation: Institute of Experimental Immunology, Laboratory of Neuroinflammation, University of Zürich, 8057 Zürich, Switzerland. k.kakalacheva@gmail.com.
authors.forename: Kristina
authors.initials: K
authors.lastname: Kakalacheva
authors.affiliation: Department of Clinical Immunology, University Hospital Zürich, 8091 Zürich, Switzerland. s.regenass@balcab.ch.
authors.forename: Stephan
authors.initials: S
authors.lastname: Regenass
authors.affiliation: Department of Pediatrics, Paracelsus Medical University Salzburg, 5020 Salzburg, Austria. s.wiesmayr@salk.at.
authors.forename: Silke
authors.initials: S
authors.lastname: Wiesmayr
authors.affiliation: Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zürich, University of Zürich, Zürich, Switzerland. azzi.tarik@gmail.com.
authors.forename: Tarik
authors.initials: T
authors.lastname: Azzi
authors.affiliation: Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zürich, University of Zürich, Zürich, Switzerland. Christoph.Berger@kispi.uzh.ch.
authors.forename: Christoph
authors.initials: C
authors.lastname: Berger
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Westmead NSW 2145, Australia. dr.russell.dale@gmail.com.
authors.forename: Russell C
authors.initials: RC
authors.lastname: Dale
authors.affiliation: Neuroimmunology Group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children's Hospital at Westmead, University of Sydney, Westmead NSW 2145, Australia. fabienne.brilot@sydney.edu.au.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Brilot
authors.affiliation: Institute of Experimental Immunology, Laboratory of Viral Immunobiology, University of Zürich, 8057 Zürich, Switzerland. muenzc@immunology.uzh.ch.
authors.forename: Christian
authors.initials: C
authors.lastname: Münz
authors.affiliation: Division of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, 45711 Datteln, Germany. K.Rostasy@kinderklinik-datteln.de.
authors.forename: Kevin
authors.initials: K
authors.lastname: Rostasy
authors.affiliation: Experimental Infectious Diseases and Cancer Research, University Children's Hospital of Zürich, University of Zürich, Zürich, Switzerland. David.Nadal@kispi.uzh.ch.
authors.forename: David
authors.initials: D
authors.lastname: Nadal
authors.affiliation: Institute of Experimental Immunology, Laboratory of Neuroinflammation, University of Zürich, 8057 Zürich, Switzerland. jan.luenemann@uzh.ch.|Department of Neurology, University Hospital Basel, 4031 Basel, Switzerland. jan.luenemann@uzh.ch.
authors.forename: Jan D
authors.initials: JD
authors.lastname: Lünemann
mesh_terms: D000293:Adolescent; D001323:Autoantibodies / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D007244:Infectious Mononucleosis / Q000150:complications* / Q000276:immunology; D008297:Male; D063308:Myelin-Oligodendrocyte Glycoprotein / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D063308:Myelin-Oligodendrocyte Glycoprotein
keywords: Epstein Barr virus; autoantibody; autoimmunity; infectious mononucleosis; multiple sclerosis