title: Epstein-Barr virus antibodies in serum and DNA load in saliva are not associated with radiological or clinical disease activity in patients with early multiple sclerosis.
abstract: OBJECTIVE
  To investigate the association of Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and viral capsid antigen (VCA) immunoglobulin (Ig)G antibodies in serum as well as EBV DNA load in saliva with radiological and clinical disease activity in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS).
  
  
  METHODS
  EBNA-1 and VCA immunoglobulin (Ig)G antibodies were determined in serum of 100 patients with CIS/early RRMS and 60 healthy controls. EBV DNA load was measured in saliva of 48 patients and 50 controls. Patients underwent clinical assessment with the Expanded Disability Status Scale (EDSS) and 3 Tesla magnetic resonance imaging at baseline and after a median of 20 months of follow-up (n = 63 for MRI, n = 71 for EDSS). The association of EBV parameters with occurrence of a second relapse, indicating conversion to clinically definite MS (CDMS), was evaluated over a median of 35 months of follow-up after the first clinical event (n = 89).
  
  
  RESULTS
  EBNA-1 IgG antibody frequency (p = 0.00005) and EBNA-1 and VCA IgG antibody levels (p<0.0001 for both) were higher in patients than in controls. EBV DNA load in saliva did not differ between groups. Neither EBV antibody levels nor DNA load in saliva were associated with baseline or follow-up number or volume of T2-weighted (T2w) or contrast enhancing lesions, number of Barkhof criteria or the EDSS, or with the number of new T2w lesions, T2w lesion volume change or EDSS change on follow-up. Likewise, levels of EBV IgG antibodies in serum and DNA load in saliva were not associated with conversion to CDMS.
  
  
  CONCLUSIONS
  While these findings confirm the association of EBV infection with early MS, neither EBNA-1 nor VCA IgG antibodies in serum nor EBV DNA load in saliva were associated with radiological or clinical disease activity in patients with CIS/early RRMS. These data are compatible with the concept that EBV may be a trigger for MS acting very early during the development of the disease.
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: René M
authors.initials: RM
authors.lastname: Gieß
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Catherina
authors.initials: C
authors.lastname: Pfuhl
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Janina R
authors.initials: JR
authors.lastname: Behrens
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Ludwig
authors.initials: L
authors.lastname: Rasche
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Freitag
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Nima
authors.initials: N
authors.lastname: Khalighy
authors.affiliation: St. Josefs-Krankenhaus, Potsdam, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Otto
authors.affiliation: NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|MIAC AG and Dep. for Biomedical Engineering, University of Basel, Basel, Switzerland.
authors.forename: Jens
authors.initials: J
authors.lastname: Wuerfel
authors.affiliation: NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Alexander U
authors.initials: AU
authors.lastname: Brandt
authors.affiliation: Labor Berlin Charité-Vivantes GmbH, Berlin, Germany.|Institute of Medical Virology, Charité -Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hofmann
authors.affiliation: Labor Berlin Charité-Vivantes GmbH, Berlin, Germany.|Vivantes Klinikum Neukölln, Berlin, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Eberspächer
authors.affiliation: NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Bellmann-Strobl
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Experimental and Clinical Research Center, Charité - Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Berlin-Buch, Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.|Clinical and Experimental Multiple Sclerosis Research Center, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Klemens
authors.identifier: http://orcid.org/0000-0003-1962-6014
authors.initials: K
authors.lastname: Ruprecht
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016022:Case-Control Studies; D004279:DNA, Viral / Q000378:metabolism*; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging* / Q000473:pathology* / Q000821:virology; D012463:Saliva / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D015415:Biomarkers; D004279:DNA, Viral