Studying MS susceptibility
to understand the role of EBV in MS
Dr Fiona McKay, from The Westmead Institute for Medical Research in
Sydney, was awarded an MS Research Australia Incubator grant in 2015.
Funded by the Trish MS Research Foundation, to support her work studying how MS risk
genes may change the way the immune system responds to the Epstein-Barr virus
(EBV) and how this might increase vulnerability to MS. Previous infection with
Epstein-Barr virus (EBV) is known to be a significant risk factors for MS.
Dr McKay conducted experiments to identify how four key MS
susceptibility genes play a role in immune cells involved in the EBV infection
pathway, and how this interaction may contribute to the onset of MS.
In order to test this, Dr McKay used DNA and immune cells collected from
individuals with MS and people without MS to examine how these MS risk genes
could be affecting the control or response to EBV infection.
This project has been extremely successful and achieved a number of
important outcomes during the one-year grant. Dr McKay and colleagues found
that three key MS risk genes were associated with increased evidence of EBV
antibodies in the blood (a sign of higher EBV activity). They also found that
the presence of the MS risks genes was associated with lower activity of other
genes in the immune cells that fight EBV infection.
Dr McKay also successfully infected B immune cells grown in the
laboratory with EBV and is currently investigating how EBV affects the
structure and function of the B cells. Following on from this project, Dr McKay
will define the effect of these risk genes on the ability of the immune system
to kill EBV-infected immune cells.
These findings provide further support for the idea that genetic
variations may underpin how an individual responds to EBV infection and
supports the growing evidence that people with MS have a reduced response to
EBV infection that leaves them vulnerable to developing MS. This research
complements the research that Professor Michael Pender at the University of
Queensland, also supported by MS Research Australia and the Trish MS Research
Foundation, has been conducting over many years. His work also reveals that
people with MS have a deficiency in the sub-type of immune cells that help
respond to EBV infection. Dr McKay’s work helps fill in some of the detail of
the mechanisms by which that might occur.
Dr McKay and her team have already published two scientific manuscripts
on their findings and have used the results from these pilot studies to
underpin a number of large grant applications to continue this research.
Ultimately this research will help narrow down the immune cell types and the
biological pathways that can be targeted to help address the imbalance in the
immune system, clear EBV infection and more effectively treat MS.