The IL7-receptor alpha gene in MS

Professor Graeme Stewart

Westmead Millennium Institute, NSW

| Better treatments | Genetics | Project | 2012 | Investigator Led Research |
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Summary

Around one-third of people with MS fail to respond to therapy with interferon beta, leaving them at increased risk of accumulating damage to the brain and spinal cord. Professor Stewart and his colleagues have previously shown that a common variant of an immune gene, the interleukin-7 Receptor alpha (IL7Rα), not only increases a person’s risk of developing MS, but leaves their immune cells unable to respond to interferon beta.

In this project, the team will compare the IL7Rα genotype of a group of people with MS who are either responders to interferon beta or non-responders. They will also examine the responses of regulatory immune cells in the blood of people with MS receiving interferon beta treatment to investigate the cellular mechanisms that underlie the effects of the IL7Rα gene variant.

If this study shows that interferon beta treatment failure is related to variations in the IL7Rα gene, then it will pave the way for a simple genetic test to identify in advance those who are likely to fail interferon beta therapy. This will allow a more effective therapy to be selected from the outset from among the growing range of alternatives.

Project Outcomes

Together with Australian collaborators, the team has collected DNA samples from approximately 1400 people who have been on interferon beta therapy. The version of the IL7Rα gene has been determined in these samples and are currently being analysed. The version of the IL7Rα gene is thought to control the gene activity in response to interferon beta, and it is likely that individuals who have the ‘hap 4’ version of the gene are not able to mount this response effectively in immune cells such as T cells and dendritic cells.

In an excellent example of the ‘multiplier effect’ that can be generated by foundation funding from MS Research Australia, the team recently secured NHMRC Project Grant funding of $606,767 for 2013-2015 to expand this project. The grant will allow them to build on the work completed in the MS Research Australia granting period and test the hypothesis that clinical response to interferon beta therapy is related to an individual’s version of the IL7Rα gene and that people with two copies of the ‘hap 4’ version are unable to mount a response. They will also determine whether the version of the IL7Rα gene is correlated with increases in specific immune cells known as regulatory T cells in MS.

Publications

  • McKay FC, Hoe E, Parnell G, Gatt P, Schibeci SD, Stewart GJ, Booth DR. IL7Rα Expression and Upregulation by IFNB in Dendritic Cell Subsets Is Haplotype-Dependent. PLoS One. 2013 Oct 16;8(10):e77508.

Updated: 13 June 2013

Updated: 06 January, 2012

Investigator

  • Professor Graeme Stewart, Westmead Millennium Institute, NSW
  • Associate Professor David Booth, Westmead Millennium Institute, NSW
  • Dr Fiona McKay, Westmead Millennium Institute, NSW
  • Associate Professor Steve Vucic, Westmead Millennium Institute, NSW

Grant Awarded

  • Project Grant

Total Funding

  • $91,600

Duration

  • 1 year over 2012

Funding Partner

  • Trish MS Research Foundation
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