Epstein-Barr-negative MS: a true phenomenon?
e318 - ?
Neurol Neuroimmunol Neuroinflamm
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Epstein-Barr virus (EBV) infection is associated with MS; up to 3.3% people with MS are EBV nuclear antigen-1 (EBNA1)-seronegative compared with 6.0% controls.1 EBV serology is complex, and multiple antigens are required to assess seropositive status.2,3 We examined a cohort of seemingly EBV-negative patients with clinically isolated syndrome (CIS). The size of the population enrolled in the International CIS study allowed us to examine the largest population of seemingly EBV-negative patients with CIS gathered to date. Methods. The International CIS study is a collaborative study across 33 centers. Inclusion and exclusion criteria and methods for sample and data collection have previously been described.4 Immunoglobulin G (IgG) reactivity against EBNA1 was initially evaluated using commercially available ELISA (ETI-EBNA-G, Diasorin, Italy) according to the manufacturer's instructions. Samples with anti–EBNA1-IgG reactivity less than the manufacturer's cutoff value (CoV) (<20 AU/mL) for the ETI-EBNA-G ELISA (screen-negative) were tested using well-validated in-house ELISAs based on multiepitope peptides of EBNA1 and virus capsid antigen (VCA) using previously described methods.5,6 The CoV for the in-house ELISA was the mean OD450 value of 4 truly EBNA1- and VCA-negative sera plus twice the SD (mean + 2 SD). OD450 values were normalized against the CoV, and values >1.0 were considered positive. Samples demonstrating negative or borderline (0.8–1.2) results against both EBV antigens were investigated using an EBV-specific immunoblot.5 Results. Patient details are provided in the table. The CIS cohort has previously been described in detail.4 Forty-one (3.9%) of 1,047 patients were screen-negative. Age, sex, time to serum sampling and clinically definite MS (CDMS) and follow-up duration were not different to the whole cohort. Screen-negative patients were less likely to be CSF oligoclonal band (OCB)-positive (48.8% vs 74.3%; p = 0.0009, Fisher exact test) and less likely to be smokers (p = 0.01). Anti–cytomegalovirus (CMV)-IgG4–negative patients were not less likely to be OCB-negative (52% vs 48%).