B-219 High seroprevalence but low frequency of intrathecal anti-Epstein-Barr virus IgG suggests a unique role of Epstein-Barr virus infection in multiple sclerosis

Abstract

Multiple sclerosis (MS) is strongly associated with high anti-Epstein-Barr virus (EBV) IgG seroprevalence. Many patients with MS have an intrathecal production of antiviral antibodies, which can be detected by elevated antibody indices (AI) [1,2]. In fact, the detection of intrathecal antibodies against measles, rubella, or varicella zoster (MRZ) viruses helps in the differential diagnosis of MS. Here, we compared the frequency of elevated AIs for anti-EBV IgG with that of other microbes in patients with MS who were seropositive for the respective antimicrobial antibodies. The presence of IgG antibodies against EBV and Borrelia burgdorferi, cytomegalovirus, herpes simplex virus 1/2, MRZ virus, parvovirus B19, tick-borne encephalitis virus, mumps virus and Toxoplasma gondii was analyzed in paired serum and CSF samples from 50 MS patients using ELISAs (all Euroimmun). The prevalence of anti-EBV IgG in serum was 100% (50/50) while the frequency of elevated EBV-AIs was 10% (5/50) resulting in a seroprevalence-corrected frequency of 0.1. The prevalence of IgG against the other microbes in serum varied from 6.0% (Borrelia burgdorferi) to 94% (varicella zoster virus) while elevated AIs ranged between 0.0% (tick-borne encephalitis virus) to 73% (parvovirus B19, MRZ around 40%). The resulting seroprevalence-corrected frequencies ranged from 0.14 (herpes simplex virus 1/2) to 1.4 (parvovirus B19, MRZ virus around 0.45). These data demonstrate a universal seroprevalence but a paradoxically low frequency of elevated AIs for anti-EBV IgG in patients with MS, in contrast to all other microbial pathogens tested. Hypothetically, pre-existing antibody-producing B cells may be primed to enter the CNS during and due to acute EBV infection, that is, at a time point before anti-EBV antibody producing cells are formed. Furthermore, combining MRZ parameters with parvovirus B19 could improve the sensitivity of the MRZ reaction for MS.