Intrathecal EBV antibodies are part of the polyspecific immune response in multiple sclerosis

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. Neurology (R) 2011;76:1316-1321