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Combined effects of smoking, anti-EBNA antibodies, and HLA-DRB1*1501 on multiple sclerosis risk


Simon, KC and van der Mei, IAF and Munger, KL and Ponsonby, A and Dickinson, J and Dwyer, T and Sundstrom, P and Ascherio, A, Combined effects of smoking, anti-EBNA antibodies, and HLA-DRB1*1501 on multiple sclerosis risk, Neurology, 74, (17) pp. 1365-1371. ISSN 0028-3878 (2010) [Refereed Article]

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Copyright © 2010 by AAN Enterprises, Inc.

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DOI: doi:10.1212/WNL.0b013e3181dad57e


Objective: To examine the interplay between smoking, serum antibody titers to the Epstein-Barr virus nuclear antigens (anti-EBNA), and HLA-DR15 on multiple sclerosis (MS) risk. Methods: Individual and pooled analyses were conducted among 442 cases and 865 controls from 3 MS case-control studies-a nested case-control study in the Nurses' Health Study/Nurses' Health Study II, the Tasmanian MS Study, and a Swedish MS Study. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for the association between smoking, anti-EBNA titers, HLA-DR15, and MS risk. Study estimates were pooled using inverse variance weights to determine a combined effect and p value. Results: AmongMScases, anti-EBNA titers were significantly higher in ever smokers compared to never smokers. The increased risk of MS associated with high anti-EBNA Ab titers was stronger among ever smokers (OR 3.9, 95% CI 2.7-5.7) compared to never smokers (OR 1.8, 95% CI 1.4-2.3; p for interaction 0.001). The increased risk of MS associated with a history of smoking was no longer evident after adjustment for anti-EBNA Ab titers. No modification or confounding by HLA-DR15 was observed. The increased risk of MS associated with ever smoking was only observed among those who had high anti-EBNA titers (OR 1.7, 95% CI 1.1-2.6). Conclusions: Smoking appears to enhance the association between high anti-EBNA titer and increased multiple sclerosis (MS) risk. The association between HLA-DR15 and MS risk is independent of smoking. Further work is necessary to elucidate possible biologic mechanisms to explain this finding.

Item Details

Item Type:Refereed Article
Research Division:Health Sciences
Research Group:Epidemiology
Research Field:Epidemiology not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:van der Mei, IAF (Professor Ingrid van der Mei)
UTAS Author:Ponsonby, A (Professor Anne Ponsonby)
UTAS Author:Dickinson, J (Professor Joanne Dickinson)
UTAS Author:Dwyer, T (Professor Terry Dwyer)
ID Code:65306
Year Published:2010
Web of Science® Times Cited:109
Deposited By:Menzies Institute for Medical Research
Deposited On:2010-10-28
Last Modified:2022-07-07

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