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Investigators Explore MS Risk Conferred by Combination of Gene and Virus

Investigators Explore MS Risk Conferred by Combination of Gene and Virus

A new study suggests that if a person has a specific gene and has high serum levels of antibodies to a specific virus, the person’s risk of developing multiple sclerosis is greatly magnified, much more than having either risk factor alone. Drs. Philip De Jager, Alberto Ascherio and colleagues from Harvard and other institutions found that those with two previously identified MS risk factors – an immune gene known as HLA DR15 and antibodies to the Epstein-Barr virus in the blood serum – were nine times more likely to develop MS than those without that gene and with low levels of viral antibodies. The study, published in a special MS-themed issue of the journalNeurology(70:1113-18March 25, 2008 Part 2), underscores the importance of studying as yet little understood interactions between genes and the environment that contribute toMS susceptibility.

Background:

MS is thought to occur when people whose genes make them susceptible encounter something in their environment that triggers this immune-based neurological disease. Although several genes probably contribute to susceptibility, specific genes that have been shown to confer higher susceptibility to MS are called HLA DR15, which help control how the immune system identifies targets. Many infectious agents have been investigated at various times as possible triggers of MS, but no single virus or bacterium has been proved to cause the disease. However, previous studies have suggested that a past history of infectious mononucleosis (caused by the Epstein-Barr virus, or “EBV”) or high levels of blood serum antibodies that fight EBV increase the risk for developing MS.

This Study:

In this study, the investigators used data from the ongoing Nurses’ Health Studies, which are questionnaire-based series that track risk factors of chronic diseases in female nurses. They focused on 148 women with MS who were enrolled in the study and who had provided blood samples for the study, and matched those cases with 296 nurses without MS who had also given blood samples. Using the samples of blood serum, they identified those with HLA DR 15 genes, and also measured for EBV antibodies. As in previous studies, they found that having HLA DR15 genes increased a person’s risk of MS from two to nearly three times than those without the genes. Also confirming previous findings, those with high levels (four times the normal level) of EBV antibodies had up to twice the risk of developing MS. What was new in this study is that they compared MS risks in those with both or neither risk factor. They found that women with both HLA DR15 and high levels of EBV antibodies were nine times as likely to develop MS than women who did not have the gene and had low levels of antibodies.

Implications:

Further research is required to confirm the findings from this relatively small study, and to determine whether they apply to other populations, including men. Also, even if these risk factors combine to increase some people’s risk of developing MS, that risk is still quite small. However, this approach is important because it looks at the combined impact of risk factors in MS, a complex disease that has thus far yielded multiple and sometimes conflicting results as to risk factors and how they might cause the disease.

In an editorial accompanying this article, Dr. Ruth Ann Marrie (University of Manitoba, Winnepeg) comments on the importance of doing studies like this one. She notes that one possible reason why studies focusing on single risk factors have been inconsistent in MS may be that MS involves “multiple, interacting risk factors from both the genetic and environmental realms.” In line with this, one of the top research priorities identified by a recent National MS Society task force on the epidemiology of MS are studies of the interactions between MS genes and possible environmental triggers.