title: Intrathecal EBV antibodies are part of the polyspecific immune response in multiple sclerosis.
abstract: OBJECTIVE
  One mechanism underlying the link between multiple sclerosis (MS) and Epstein-Barr virus (EBV) might be a direct CNS infection. Viral CNS infections cause elevated antibody indices (AIs). Elevated EBV AIs were found in MS; however, patients with MS frequently show a polyspecific intrathecal immune response with elevated antiviral AIs. To discriminate whether elevated EBV AIs indicate a virus-driven or a polyspecific intrathecal immune response, we determined the intrathecal fraction of anti-EBV antibodies.
  
  
  METHODS
  The fraction of intrathecally synthesized EBV-specific immunoglobulin G (IgG) of the total intrathecally synthesized IgG (F(S) anti-EBV) was determined in 24 patients with a clinically isolated syndrome (CIS) or MS and 3 patients with cerebral posttransplantation lymphoproliferative disorder (PTLD), all of whom had elevated EBV AIs. F(S) anti-measles and AIs for measles, rubella, varicella zoster, and herpes simplex virus were measured as well. The prevalence of an elevated EBV AI was analyzed in another 36 patients with CIS.
  
  
  RESULTS
  Median F(S) anti-EBV in patients with CIS/MS was low (0.65%) and did not differ from F(S) anti-measles (0.9%). Median F(S) anti-EBV was about 40-fold higher in patients with cerebral PTLD than in patients with CIS/MS. All 24 patients with CIS/MS with an elevated EBV AI had at least one further elevated antiviral AI. Only 2 of 36 (5.6%) patients with CIS showed an intrathecal synthesis of anti-EBV antibodies.
  
  
  CONCLUSIONS
  Intrathecally produced anti-EBV antibodies are part of the polyspecific intrathecal immune response in CIS/MS and only rarely detectable in patients with CIS, both arguing against a direct CNS infection with EBV in patients with CIS/MS.
authors.affiliation: Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Otto
authors.forename: A
authors.initials: A
authors.lastname: Oltmann
authors.forename: A
authors.initials: A
authors.lastname: Stein
authors.forename: K
authors.initials: K
authors.lastname: Frenzel
authors.forename: J
authors.initials: J
authors.lastname: Schroeter
authors.forename: P
authors.initials: P
authors.lastname: Habbel
authors.forename: B
authors.initials: B
authors.lastname: Gärtner
authors.forename: J
authors.initials: J
authors.lastname: Hofmann
authors.forename: K
authors.initials: K
authors.lastname: Ruprecht
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000918:Antibody Specificity; D001927:Brain Diseases / Q000209:etiology / Q000276:immunology; D015331:Cohort Studies; D003711:Demyelinating Diseases / Q000276:immunology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology; D008297:Male; D008457:Measles / Q000276:immunology; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D013116:Spinal Cord / Q000276:immunology; D019737:Transplants / Q000009:adverse effects; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G