Research has revealed that there are over 110 genes which increase the risk of a person developing MS. One of these genes is called IL2RA. A group of Australian MS researchers have developed a new method for studying the activity of individual genes.
In this study, published in the highly prestigious journal Genes and Immunity, a number of MS Research Australia supported researchers, including Dr Andrew Fox, investigated how special ‘chemical tags’ can affect the activity of the gene IL2RA.
The researchers developed an innovative mathematical modelling technique called deconvolution to obtain these results.
Human blood contains a range of cells, some of which are immune cells. Immune cells, as a whole, can be isolated from blood relatively easily, however, it is more difficult to separate out specific types of immune cell from the entire blood. But to really understand what is happening in MS it is crucial for researchers to be able to tease out how different genetic changes affect very specific sub-groups of immune cells.
So to get around this problem of physically separating out the many different types of immune cells, the team developed a clever mathematical technique, to extract information that was specific to T cells, a type of immune cell, from data gathered from the entire group of blood immune cells.
Humans are estimated to have around 20,000 genes. Each gene is found in every cell type in the body but is very tightly regulated, so that it only switches on and off as a specific cell type needs to use it. One way of controlling gene activity is by a process called ‘DNA methylation’. This is where a chemical tag is added to the DNA in order to flag that it should be switched on or off. Abnormalities in DNA methylation have been reported to play a role in other autoimmune disorders such as Type 1 Diabetes and Lupus.
When the group looked at DNA methylation in all the immune cells in the blood they did not find any differences between people with or without MS. However, when they used their mathematical modelling technique to specifically focus on T cells, they discovered that the DNA methylation patterns were different in people with MS compared to those that did not have MS. This result was only observed in T cells, and not in other immune cells.
These changes in DNA methylation are likely to result in more IL2RA protein being made, in the T cells of people with MS. T cells play a crucial role in the inflammation of the brain and spinal cord, characteristic of MS. In T cells, it is thought that IL2RA results in the T cells becoming more “active” and promoting inflammation in the brain.
The development of this technique opens up an exciting and very important new avenue of research that will allow a much deeper understanding of how genes and the environment interact to contribute to the development of MS. Based on this research, further studies are required to determine whether difference in DNA methylation exist in other genes and cell types, and if these difference result in changes to the protein and its ultimate effects in people with MS.