Epstein-Barr Virus Positivity Linked to Increased Interaction Between Smoking and MS

Emma Hitt, PhD

April 09, 2010

April 9, 2010 — Smoking appears to be associated with an increased risk of multiple sclerosis (MS) in individuals with high anti–Epstein-Barr virus nuclear antigens (EBNA) titers but not in those with low titer levels, according to a report in the April 7 online issue of Neurology.

Claire Simon, ScD, with Harvard School of Public Health in Boston, Massachusetts, and colleagues evaluated data from 3 case-control studies involving 442 MS cases and 865 controls. The 3 studies were a nested case-control study in the Nurses’ Health Study/Nurses’ Health Study II, a Tasmanian MS study, and a Swedish MS study.

“Few studies have considered the effects of MS risk factors simultaneously,” Dr. Simon told Medscape Neurology. “Our goal was to investigate whether the observed effects of smoking, anti-EBNA antibody titers, and HLA-DR15 were independent or related, indicating the possibility of shared biological mechanisms,” she said. 

The current analysis used data from 3 case-control studies, a nested case-control study in the Nurses' Health Study I and II, a Tasmanian MS study, and a Swedish MS study, including 442 subjects with MS and 865 without MS.

The investigators found that among patients with MS, anti-EBNA titers were much higher among smokers than among nonsmokers. In addition, the increased risk of MS associated with anti-EBNA was stronger among those who had ever smoked (odds ratio [OR], 3.9; 95% confidence interval [CI], 2.7 – 5.7) compared with never smokers (OR, 1.8; 95% CI, 1.4 – 2.3; P value for interaction = .001).

By contrast, the association between smoking and MS was not present in individuals with low anti-EBNA titer levels. In addition, the risk of MS associated with smoking did not appear to be modified by HLA-DR15 gene status.

A Common Biologic Pathway

According to Dr. Simon, the findings may be informative for generating hypotheses as to how these known risk factors are related to pathological changes that ultimately result in MS.

In the "Discussion" section of the paper, the researchers note that the findings support the hypothesis of a common biologic pathway whereby some component of cigarette smoke modulates either Epstein-Barr virus (EBV) infection or the host immune system’s response to EBV infection.

“Our data support a supermultiplicative effect suggesting that the association between high anti-EBNA immunoglobulin G Ab titers and MS risk is enhanced by smoking,” Dr. Simon and colleagues add.

Importance of Smoking Cessation

Dr. Simon pointed out that smoking is a modifiable factor and known to be detrimental for several health outcomes. It has been consistently associated with risk for MS and worse progression for those with MS. 

“To my knowledge, there is not a well-described causative mechanism linking smoking and MS,” she said. “Possible mechanisms, such as neurotoxicity and immunomodulatory effects, have been suggested, but there is limited data on this topic.”

Asked for comment on these findings, Lily Jung, MD, with the Swedish Neuroscience Institute, in Seattle, Washington, added that recent studies show that not only does smoking increase risk of developing MS, it also increases magnetic resonance imaging lesion volume and brain atrophy and leads to faster progression of the disease.

“We should be screening our patients for their smoking history and counseling them on the importance of smoking cessation,” Dr. Jung told Medscape Neurology. “This should not just be left to the primary care providers; [MS specialists] should also be actively discouraging smoking,” she said.

Dr. Jung noted that the findings may be interpreted to mean that if a person has not been exposed to EBV, they can smoke and not risk developing MS. “However, the rate of exposure to EBV in the general population is high, so that argument is not valid.”

The study was supported by the National Institutes of Health, the National Health and Research Council of Australia, the Australian Rotary Health Research Fund, and MS Australia. Dr. Simon and Dr. Jung have disclosed no relevant financial relationships.

Neurology. Published online April 7, 2010.

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