Revealing the 'rogue clones' that cause lupus

Flinders University researchers have revealed the structure of ‘rogue clones’ (also known as autoantibodies) that cause lupus, in a medical breakthrough which could help identify early signs of the debilitating autoimmune disease and develop effective treatments.

When a person suffers from lupus, their immune system cannot tell the difference between foreign invaders and their own healthy tissues. The result is an autoimmune attack causing severe fatigue, joint pain, skin rashes and damage to kidneys, lungs, the brain and blood vessels. Symptoms and severity can depend on individual circumstances, with Adelaide-based lupus sufferer Amy Strawbridge describing the disease as “mentally debilitating”.

“I get bald patches in my hair; rashes on my face, which can be quite embarrassing at times; and extreme tiredness, regardless of how much I sleep,” she said.

“You feel so helpless when you have lupus.”

Professor Tom Gordon, Head of Immunology at Flinders University and Clinical Director of Immunology at SA Pathology, said up to 20,000 Australians suffer from lupus, with 1.5 million people affected in the US and 5 million worldwide.

“Lupus can present in hundreds of different and unpredictable ways, making the diagnosis difficult — particularly when you consider that the methods for measuring anti-dsDNA autoantibodies are decades old and give no information on their molecular composition,” he said.

The good news is that Prof Gordon and his team at Flinders have found a way to use mass spectrometry to identify and track down the molecular signatures of these autoantibodies, which could lead to earlier diagnosis and more effective treatments. The results of their work have been published in the journal Clinical & Experimental Immunology.

“We have advanced from measuring the level of autoantibody to breaking down their precise clonal components,” Prof Gordon said. “Identifying and isolating the signature of these rogue clones can provide information about whether a drug therapy is working or not.”

“The ultimate goal of our work is to measure response to treatment and to design therapies to remove rogue clones we measure in individual lupus patients,” added co-author Dr Jing Jing Wang, who received a Commendation in the 2018 Bupa Health Foundation Emerging Health Researcher Awards for her work identifying molecular signatures to help tackle autoimmune diseases.

It may therefore be possible to associate particular clones to symptoms of the disease and organ involvement while identifying new treatments before they cause irreversible damage. According to Prof Gordon, “We are now in a position to identify which rogue clones are responsible for inflammation and potential damage in different organs, and perhaps discover clones that protect against dangerous complications.

“We can now focus on developing targeted novel therapies aimed at removing rogue cells in the blood, to prevent it from ever forming its own army of clones, effectively stopping the disease before it takes hold completely.”

Image credit: ©stock.adobe.com/au/9nong

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