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: Among MS cases, 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.
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: Among MS cases, 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.
Authors: W Henle; G Henle; J Andersson; I Ernberg; G Klein; C A Horwitz; G Marklund; L Rymo; C Wellinder; S E Straus Journal: Proc Natl Acad Sci U S A Date: 1987-01 Impact factor: 11.205
Authors: Marc Jacobsen; Sabine Cepok; Elfriede Quak; Michael Happel; Rami Gaber; Andreas Ziegler; Sabine Schock; Wolfgang H Oertel; Norbert Sommer; Bernhard Hemmer Journal: Brain Date: 2002-03 Impact factor: 13.501
Authors: Ellen T Chang; Tongzhang Zheng; Evelyne T Lennette; Edward G Weir; Michael Borowitz; Risa B Mann; Donna Spiegelman; Nancy E Mueller Journal: J Infect Dis Date: 2004-05-21 Impact factor: 5.226
Authors: P Sundström; P Juto; G Wadell; G Hallmans; A Svenningsson; L Nyström; J Dillner; L Forsgren Journal: Neurology Date: 2004-06-22 Impact factor: 9.910
Authors: Adam E Handel; Alexander J Williamson; Giulio Disanto; Lahiru Handunnetthi; Gavin Giovannoni; Sreeram V Ramagopalan Journal: PLoS One Date: 2010-09-01 Impact factor: 3.240
Authors: Adam E Handel; Lynne Jarvis; Ryan McLaughlin; Anastasia Fries; George C Ebers; Sreeram V Ramagopalan Journal: PLoS One Date: 2011-01-27 Impact factor: 3.240
Authors: D Csuka; D Simon; R Hóbor; K Uray; Z Prohászka; Z Bánlaki; P K Jani; Á Szilágyi; F Hudecz; K Rajczy; G Beke; A Boros Major; A Tordai; Z Illés; T Berki; L Czirják; G Füst Journal: Clin Exp Immunol Date: 2013-03 Impact factor: 4.330