I am giving a debate at the MS Frontiers
meeting taking place 23-24 June 2011 at Sofitel , Heathrow. The following is my abstract.
"Multiple Sclerosis is caused by Epstein Barr virus"
"Is there sufficient data to support EBV as being the cause of MS? Clearly, further research is required to disprove the hypothesis. Is it premature and irresponsible to make claims of causation? People with MS feel that the issues around EBV are very complex and difficult to interpret, and that there are too many unanswered questions to support the claim that “EBV is the possible cause of MS”. It is clear that MS is a complex disease, i.e. it results from an interaction between genes and the environment. The majority of the genetic susceptibility to MS is linked to specific MHC haplotypes. Migration studies indicate that exposure to an environmental factor(s) in early adolescence or childhood causes or contributes to the cause of MS. The incidence of MS is increasing. In some populations the female:male sex ratio of people affected with MS has gradually been increasing. Smoking, levels of sunlight exposure (latitude), vitamin D metabolism and season of birth are other factors that are associated with MS risk. If EBV causes MS all these factors have to be explained. In contrast the evidence for other causative factors is less well established. The following are some of the reasons that support the claim that EBV causes MS:
Despite this evidence EBV does not fulfil Koch’s postulates, but does fulfill many contemporary criteria for causation. Causation, however, is a complex science and more extensive and definitive data is required to convince the wider community that EBV is the pivotal factor in the complex causal pathway that ultimately leads to the development of MS. To establish EBV as the cause of MS all aspects of the epidemiology of MS and specific clinical observations will need to be explained or at least be concordant with the hypothesis; for example response to specific classes of disease-modifying therapies. Establishing the causal link between EBV infection and MS will provide several new therapeutic and preventative strategies for people and their families living with the disease."
- Virtually all subjects with MS (>99%) are infected with EBV compared to only ~90% of control subjects.
- MS is very rare in subjects who are not infected with EBV.
- People with MS have an increased tendency for spontaneous in-vitro lymphocyte transformation.
- People who have had symptomatic EBV infection or glandular fever have a higher risk of developing MS compared to people who have not had glandular fever (relative risk ~2.4).
- People with higher levels of antibodies to EBV have a higher risk of developing MS compared to subjects with low antibody levels.
- A unusual cluster of MS in children attending a school in rural Denmark occurred shortly after an outbreak of glandular fever.
- A undefined proportion of antibodies in the spinal fluid of subjects with MS recognise EBV-specific.
- Autoimmune MBP-specific T cells in the circulation of subjects with MS, which are capable of orchestrating an attack on myelin producing cells, also recognise EBV antigens.
- Subjects with MS have a higher number of circulating T cells that recognise EBV than controls subjects.
- There is evidence that during MS relapses EBV is actively replicating compared to period of remission MS, suggesting that MS relapses or disease activity may be triggered by peripheral EBV replication.
- Drugs that target B-cells are effective in MS.