Our research into Guillain-Barré syndrome (GBS) starts with understanding the mechanisms of autoimmune diseases and delves in to more specific areas such as genetics and the role of B cells. We've been able to determine the series of events that lead from an infection to developing an autoimmune disease, a process that was not understood before.
The use of immunology crossed with genomics will allow us to study patients with GBS and whether they have particular genetic defects that made them predisposed to the syndrome. We're also looking to understand the changes in the body’s immune system from infection to GBS, focusing on B cells and the antibodies they produce. This information could then be used to develop treatments that could halt and reverse disease progress.
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Key areas of investigation
Garvan’s Professor Chris Goodnow believes there may be a common cause underlying autoimmune diseases. These are ‘rogue clones’ – rogue immune cells circulating and causing tissue and organ damage as the body attacks itself.
The Hope Research project will identify bad mutations in cells (which result in rogue cells), and use sophisticated cellular genomic technology to determine exactly what each cell is doing, instead of guessing by studying large groups of cells.
We can then pinpoint chinks in the armour of the rogue clones, hopefully making them susceptible to new drugs and immunotherapy. We'll study study 44 autoimmune diseases (including GBS) in this way.
Amanda Russell has been using Whole Genome Sequencing (WGS) to look for germline variants, which are mutations in reproductive cells that can be passed on to offspring, that indicate a higher risk of developing GBS. Next Generation Sequencing (NGS) has also been used on the same patients to study the patient’s B cells and their receptors, to search for the B cells responsible for peripheral nerve damage.
Deborah Burnett has been given the task of leading the GBS part of the Hope Research project to start later this year. The cerebrospinal fluid of newly diagnosed, untreated GBS patients will be collected to study using NGS. They will also be studying how the B cells develop antibodies in response to pathogens that have very similar cell surface proteins to cells in humans. This will allow them to see how these antibodies can be developed without causing an autoimmune response, and to compare this to how antibodies develop in GBS.
Understanding the above mechanisms is the first step in unlocking treatments with the potential to stop and reverse GBS.
National and international collaborations
- National Health and Medical Research Council, Canberra, Australia
- The Bill and Patricia Ritchie Foundation, Sydney, Australia
- Weizmann Institute of Science, Rehovot, Israel
- Westmead Hospital, Sydney, Australia