Multiple sclerosis (MS) is a condition that affects the brain and the spinal cord where the coating (myelin) that protects the nerves becomes damaged. The damage to the myelin is thought to be caused by an attack from the immune system. This attack may be caused by a reaction to a virus such as Epstein-Barr virus which is a common virus from the herpes virus family. Once infected with this virus, it can be detected in the blood for a number of years. Recently, results from a study US military personnel showed that people infected with EBV were 32 times more likely to develop MS compared to those who tested negative for EBV. This suggests that EBV could be a major cause of MS; however, in order to confirm this it is important that these findings are replicated in other studies.
We will use data from blood tests and diagnoses in people in the large primary care database the clinical practice research database(CPRD). We will examine whether those who test positive for EBV or have previously had a diagnosis of EBV have a greater risk of developing MS in the UK. If confirmed, this may establish infection with EBV as a major cause of MS which in turn, will allow us to design better treatments for those with MS.
Multiple sclerosis is a chronic inflammatory disease where there is progressive demyelination of the central nervous system. This can lead to severe neuronal dysfunction causing disability and a marked reduction in the quality of life in those with MS. There is evidence to support an infectious cause of MS with results from a recent analysis of a US military prospective cohort showing a 32-fold higher risk of MS in those who tested positive for EBV compared to age and sex matched controls who tested negative for EBV. In order to establish EBV as a major cause of MS it is important that these findings are reproduced in other studies. We propose to examine this association in the Clinical Practice Research Database.
Our objective is to assess the risk of developing MS in people with a Read/SNOMED code indicating EBV exposure compared to those with a negative test result for EBV. We will use a matched cohort study in a population aged 18 years and older registered with a GP practice inputting data to CPRD GOLD and AURUM between 1995 and 2021. EBV exposure will be defined as a relevant Read code/SNOMED code and these patients will be matched by age, sex and GP practice to those without such a code in their record. Using the same method we will also assess the risk of MS in those with a code indicating cytomegalovirus (CMV) exposure as a negative control. We will use Cox regression to examine the risk of a subsequent multiple sclerosis diagnosis adjusting for sociodemographic and other confounding variables.
The main outcome of this analysis is new multiple sclerosis diagnosis. We will use clinical codes for multiple sclerosis that are listed in the Appendix.
Krishnarajah Nirantharakumar - Chief Investigator - University of Birmingham
Zhaonan Wang - Corresponding Applicant - University of Birmingham
Eleanor Hathaway - Collaborator - University of Birmingham
Francesca Crowe - Collaborator - University of Birmingham
Joht Singh Chandan - Collaborator - University of Birmingham
Practice Level Index of Multiple Deprivation;Patient Level Townsend Index