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Unearthing the basis of autoimmune disease

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4 May 2017

Goodpasture-1-400px.jpg
Illustrator: Vanette Tran - In Goodpasture’s disease when the molecule DR15 is present it can select and instruct T cells to attack the body. But when people also have the protective DR1 molecule present these T cells are held at bay and can be overturned.

Monash University researchers have discovered the mechanism that explains how key genetic risk factors cause or protect people from autoimmune disease such as type 1 diabetes, multiple sclerosis, and Crohn’s disease.

Published overnight in Nature, Monash researchers have answered the fundamental question: why, and how, does having different immune molecules change a person’s underlying genetic risk of developing an autoimmune disease?

Autoimmune diseases affect over 1 million Australians and, in the Western world, are a leading cause of death in women under the age of 65. These diseases include type 1 diabetes, multiple sclerosis, Crohn’s disease, ulcerative colitis, rheumatoid arthritis and several types of kidney disease.

Monash University co-senior author, Professor Richard Kitching, explained that our immune system has evolved to fight infections and disease.

“Our immune system is able to protect us from foreign invaders, as it learns to recognise different infections over time,” Professor Kitching said.

“But, this sometimes goes wrong and our immune system recognises parts of our own body as being foreign. This leads to autoimmune disease.”

Professor Jamie Rossjohn, co-senior author, ARC Laureate Fellow, Head of the Infection & Immunity Program at Monash's Biomedicine Discovery Institute and Chief Investigator on the ARC Centre of Excellence in Advanced Molecular Imaging, said that autoimmune diseases occur when our immune system produces an aberrant response against our own cells, tissues and/or organs, resulting in inflammation and damage.

“Certain immune molecules, called HLA molecules, are associated with an increased genetic risk to cause autoimmunity, whereas other HLA molecules can protect from disease,” Professor Rossjohn said.

Professor Kitching said their research provided the first mechanistic evidence of the basis of protective and disease causing HLA molecules in autoimmunity.

“Our research has given us a new understanding of why some people are at risk of disease, while others are protected,” Professor Kitching said.

“We have known that in autoimmune diseases there are T cells that make us susceptible to disease and T cells that protect us from disease. Now we know how this happens; it opens the field for new and more targeted treatments to specific diseases.

“In Goodpasture’s disease when the molecule DR15 is present it can select and instruct T cells to attack the body. If alone in our body these damaging cells can attack the body’s tissues, resulting in very ill patients.

“But when people also have the protective DR1 molecule present these T cells are held at bay and can be overturned,” Professor Kitching said.

This research is the first mechanistic evidence of what causes our immune system to go rogue and attack parts of our own body. It paves the way for further research and for new and novel treatments, as well as avenues that lead to personalised therapies.

“We have answered one of the biggest questions in autoimmune disease,” Professor Rossjohn said.

“There is evidence out there that this mechanism is relevant to other autoimmune diseases and it opens up new lines of research into how autoimmune disease occurs.”

“These particular protective immune cells are specific and are extremely powerful,” Kitching continued. “So, if we can encourage them to develop in the body, or expand people’s cells outside the body and inject them back into those with disease, this could result in better and more targeted treatments for autoimmune diseases,” he said.

Watch the animation below which illustrates the DR1 molecule at work.

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For interview:

Richard Kitching

Media contact:

Stephanie Pradier, +61 (0) 4 24 568 314, stephanie.pradier@moansh.edu

Further information

**Professor Richard Kitching is a clinician-scientist and the director of the Monash Centre for Inflammatory Diseases

About the Monash Centre for Inflammatory Diseases (CID)

Research in the Monash University Centre for Inflammatory Diseases spans basic experimental biology, clinical research and clinical practice in inflammatory diseases. We use both clinical and laboratory based experimental techniques to explore the mechanisms of inflammatory injury in important human diseases - and then relate these to unmet needs in patient treatment and management. Researchers within the Centre are expert in laboratory based and clinically focused research.

**Professor Jamie Rossjohn is the Head of the Infection & Immunity Program at the Monash Biomedicine Discovery Institute and a Chief Investigator on the Australian Research Council Centre of Excellence in Advanced Molecular Imaging

About the Australian Research Council Centre of Excellence in Advanced Molecular Imaging

The $39 million ARC-funded Imaging CoE develops and uses innovative imaging technologies to visualise the molecular interactions that underpin the immune system. Featuring an internationally renowned team of lead scientists across five major Australian Universities and academic and commercial partners globally, the Centre uses a truly multi scale and programmatic approach to imaging to deliver maximum impact. The Imaging CoE is headquartered at Monash University with four collaborating organisations – La Trobe University, the University of Melbourne, University of New South Wales and the University of Queensland.