Integrating risk factors: HLA-DRB1*1501 and Epstein-Barr virus in multiple sclerosis.
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 148 women with MS (18 with blood collected before disease onset) and 296 age-matched healthy women 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.


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.
De Jager
P L
PL
Center for Neurologic Diseases, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Simon
K C
KC
Munger
K L
KL
Rioux
J D
JD
Hafler
D A
DA
Ascherio
A
A
D000328:Adult; D000906:Antibodies / Q000032:analysis / Q000097:blood / Q000276:immunology; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D015897:Comorbidity; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology; D005260:Female; D005787:Gene Frequency / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006684:HLA-DR Antigens / Q000097:blood* / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D004854:Herpesvirus 4, Human / Q000276:immunology; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000235:genetics / Q000276:immunology*; D012307:Risk Factors
D000906:Antibodies; D015415:Biomarkers; D019309:Epstein-Barr Virus Nuclear Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C417029:EBV-encoded nuclear antigen 1