COPENHAGEN—The interaction between smoking and Epstein–Barr virus (EBV), two risk factors for multiple sclerosis (MS), may depend on age, according to research presented at the 29th Congress of the European Committee for Treatment and Research in MS. Smoking and EBV appear to have a negative interaction in adults younger than 26 and a positive interaction in adults older than 26.
“The negative interaction in younger subjects suggests that EBV and smoking as risk factors for MS act independently from an etiologic perspective,” said Jonatan Salzer, MD, PhD, a physician at Umeå University in Sweden. “The positive interaction in older subjects may suggest that the two risk factors share a common pathophysiologic pathway, most obviously that smoking enhances the antibody response against EBV after several years with MS.”
Analysis of Prospectively Collected Blood Samples
In a nested case–control study, Dr. Salzer and colleagues analyzed prospectively collected biobank blood samples. Of the patient population, 192 persons subsequently developed MS and 384 participants served as matched controls. The researchers measured levels of cotinine, a nicotine metabolite, in the samples with an immunoassay. Anti-EBNA-1 IgG antibodies were measured using an enzyme-linked immunosorbent assay (ELISA).
The investigators considered participants with cotinine levels of 10 ng/mL or higher to be smokers. The group also divided anti-EBNA-1 IgG levels at the median among controls. Dr. Salzer and colleagues assessed interaction on the additive and multiplicative scales and estimated the effects of the risk factors across strata of each other.
Smoking and EBV Did Not Interact Significantly
When analyzing the entire cohort, the researchers found no statistically significant interactions between smoking and EBV. The mean level of anti-EBNA-1 IgG was higher among subjects with cotinine levels of 10 ng/mL or higher than among participants with cotinine levels lower than 10 ng/mL. The investigators found no heterogeneity of effects of one risk factor across strata of the other. When the researchers analyzed interaction on the additive and multiplicative scales, they found that the group of patients with both risk factors (ie, high levels of anti-EBNA-1 IgG and cotinine level of 10 ng/mL or greater) had a slightly higher odds ratio of MS than predicted by the independent effects of the risk factors.
An analysis restricted to younger subjects indicated that the odds ratio for the patients with both risk factors was in between that of the additive interaction and that of the multiplicative interaction. The effects of both risk factors showed nonsignificant signs of heterogeneity, however. Among older patients, the pattern of heterogeneity of effects across strata was the opposite of that among younger patients, the researchers reported.
—Erik Greb