Integrating risk factors. 

HLA-DRB1*1501 and Epstein-Barr virus in multiple sclerosis.

 ABSTRACT BACKGROUND:

Individuals with high levels of antibodies to the Epstein-Barr virus nuclear antigen 1 (EBNA-1) have an increased risk of developing multiple sclerosis (MS), but this association could be confounded by genetic susceptibility. 

METHODS:

We conducted a nested case-control study including

to determine whether the human leukocyte antigen (HLA) DRB1*1501 allele (DR15) and anti-Epstein-Barr virus (anti-EBV) antibody titers are independent risk factors for MS. 

* Titers  -  The dilution of a serum containing a specific antibody at which the solution retains the minimum level of activity needed to neutralize or precipitate an antigen.

RESULTS:

The association between anti-EBNA-1 antibody titers and MS risk was not affected by adjustment for DR15 and was similar in DR15-positive and DR15-negative women.  The relative risk of MS among DR15-positive women with elevated (>1:320) anti-EBNA-1 titers was ninefold higher than that of DR15-negative women with low (<1:80) anti-EBNA-1 titers. 

CONCLUSIONS:

Anti-Epstein-Barr virus nuclear antigen 1 (anti-EBNA-1) antibody titers are a risk factor for multiple sclerosis (MS), independently from the DR15 allele.  Carriers of the DR15 allele with elevated anti-EBNA-1 antibody titers may have a markedly increased risk of MS.