Effects of infectious mononucleosis and HLA-DRB1*15 in multiple sclerosis.
BACKGROUND
Both human leukocyte antigen (HLA)-DRB1*15 and Epstein-Barr virus infection presenting as infectious mononucleosis (IM) are recognized as risk factors for multiple sclerosis (MS). However, their combined effect and possible interaction on MS risk is not known.


OBJECTIVE
To assess the association between HLA-DRB1*15 and risk of MS in persons with and without IM.


METHODS
We compared the prevalence of DRB1*15 in MS patients with (n = 76) and without (n = 1,836) IM with the corresponding distributions in blood donors with (n = 62) and without (n = 484) IM histories. This allowed us to estimate the relative risk of MS associated with DRB1*15 in the presence and absence, respectively, of previous IM. We then estimated the interaction between DRB1*15 and IM as the ratio of the two individual odds ratios.


RESULTS
In IM-naïve individuals, DRB1*15 carried a 2.4-fold (95% confidence interval [CI], 2.0-3.0) increased MS risk. In contrast, among persons with IM history, DRB1*15 was associated with a 7.0-fold (95% CI, 3.3-15.4) increased MS risk. Thus, the MS risk conferred by HLA-DRB1*15 was 2.9 (95% CI, 1.3-6.5)-fold stronger in the presence than in the absence of IM. Combined with previous results, this result indicates that DRB1*15-positive persons with a history of IM may be at a 10.0-fold (95% CI, 6.0-17.9) increased risk of MS compared with persons who are DRB1*15 and IM-naïve.


CONCLUSIONS
DRB1*15 and IM may act in synergy causing MS.
Nielsen
T R
TR
Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. trn@ssi.dk
Rostgaard
K
K
Askling
J
J
Steffensen
R
R
Oturai
A
A
Jersild
C
C
Koch-Henriksen
N
N
Sørensen
P S
PS
Hjalgrim
H
H
D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D007244:Infectious Mononucleosis / Q000453:epidemiology* / Q000235:genetics*; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D015995:Prevalence; D012307:Risk Factors
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen