Rogue cell breakthrough for auto-immune treatments

The treatment of auto-immune diseases could be revolutionised after scientists isolated the rogue cells that cause the problem.

The diagnosis and treatment of auto-immune diseases could be revolutionised after scientists for the first time isolated the rogue cells that cause the immune system to attack itself.

The researchers from the Garvan Institute of Medical Research and the University of NSW used cellular genomics technology to reveal the genetic mutations that cause immune cells to make antibodies that attack the body’s own cells — uncovering the root cause of auto-immune disease.

An estimated one in eight Australians suffers an auto-immune disease and the cause of the con­ditions has remained a mystery.

Doctors treating auto-immune diseases are currently unable to ascertain whether a treatment drug is working to eradicate rogue immune cells, and the researchers said their breakthrough could transform the management of diseases ranging from multiple sclerosis, coeliac disease, thyroid disorders and rheumatoid arth­ritis, among scores of other auto-immune conditions.

“What we know is that for any auto-immune disease, some cells, at least one cell and probably many cells, have gone rogue so that they’ve got around the normal checkpoints to attack part of the body,” said Chris Goodnow, executive director of the Garvan Institute and director of the UNSW Sydney Cellular Genomics Futures Institute. “We’ve been able to isolate the cells that have gone rogue and are really causing the disease. It opens up the way for a physician to monitor the driving cells in an auto-immune disease.

“The real problem for a doctor at the moment in any auto-immune disease is they don’t know what’s causing it. They can’t monitor the cells that are causing the disease. Without being able to see the driving cells and what’s wrong with them, there’s no ability to prioritise which drug is more likely to work,” Professor Goodnow said.

“And then even when you try a drug, the doctor has to just wait and monitor the symptoms rather than being able to see whether the drug is actually knocking off the rogue cells. This is a way to start doing that.”

The Garvan Institute-led research used single-cell genomic technology — which lets scientists analyse each cell in a ­patient sample individually and examine each cell’s DNA and RNA — to identify the rogue cells that cause auto-immune disease.

They examined four samples from people suffering cryoglobulinemic vasculitis, which develops in some people with Sjogren’s syndrome, systemic lupus, rheumatoid arth­ritis, or hepatitis C virus infection.

Once they isolated the rogue cells, they found part of that cell’s DNA carried mutations.

“We identified step-wise genetic changes in the cells at the root of an auto-immune disease for the first time, tracing an ‘evolutionary tree’ of how normal immune cells develop into disease-causing cells,” said co-senior author Joanne Reed, who heads the Gravan’s Rheumatology and Auto­immunity Group.

The genetic mutations on the rogue auto-immune cells were very similar to the mutations that blood cancer cells carry, opening up a possibility drugs that are effective in treating lymphoma may also work in treating auto-immune conditions.

The research is published in the scientific journal Cell.