Researchers at The Australian National University (ANU) in Canberra have helped identify a rare, mutated version of a protein called TNIP1 that causes a chronic autoimmune disease similar to Sjogren’s Syndrome – a condition that leads to extreme dryness of the eyes and mouth that can cause blindness if left untreated.
According to the researchers, part of an international team of scientists, the mutation may also be responsible for more severe autoimmune diseases including lupus, a debilitating condition that causes inflammation in organs and joints, skin rashes and fatigue. In extreme cases, the disease can be fatal.
The scientists say they were able to successfully reverse the damaging effects of the mutation in mice, bringing them a step closer to developing new drug therapies that do the same in humans.
The findings could lead to new and tailored treatments for Sjogren’s Syndrome and lupus that is caused by TNIP1 variants.
Lead author Dr Arti Medhavy, who completed this work as part of her PhD at ANU, said this was the first time scientists had shown a variation of the TNIP1 protein was responsible for causing autoimmune disease in humans.
“Proteins are critical to our growth, development and overall health, but they have a shelf life. Once the proteins have served their purpose, they become deactivated,” Dr Medhavy, from Griffith University’s Institute for Biomedicine and Glycomics, said.
“That’s where TNIP1 comes in. It works in unison with the cell’s waste management system. TNIP1 essentially acts as a gatekeeper of the immune system by removing obsolete proteins and taking them to the cell’s degradation sites where they are broken down, recycled and repurposed.
“But the mutated version of the TNIP1 protein is less efficient at taking these waste proteins and mitochondria to be processed, leading to toxic build-up within cells,” Dr Medhavy said.
“If this waste isn’t dealt with, these materials can become detrimental to the cell and trigger the immune system, which ultimately promotes the onset of autoimmune disease.”
It’s believed one in 10 Australians is living with some form of autoimmune disease.
Study co-author Dr Vicki Athanasopoulos, from ANU, said Sjogren’s Syndrome was a nasty and debilitating condition that affected more than 270,000 Australians.
She said there was a need to develop tailored treatments that specifically targeted the proteins and biochemical pathways that led to the onset of autoimmune disease, rather than suppressing the entire immune system.
“There is currently no cure for autoimmune disease. Current therapies help patients better manage their condition, but these treatments have unpleasant side effects that make patients more susceptible to infection, which can lower their quality of life,” Dr Athanasopoulos said.
The researchers identified the TNIP1 mutation in two unrelated patients – one from Australia and the other from China. Despite both having the same TNIP1 mutation, one patient exhibited signs and symptoms of lupus, while the other seemed to display symptoms of Sjogren’s Syndrome.
Using gene-editing technology, the researchers introduced the human equivalent TNIP1 mutation into mice. They found that mice carrying the mutation developed a condition that mimicked the Sjogren’s disease-like symptoms seen in one of the human patients.
The research is published in Nature Immunology. This work also involved scientists from the Francis Crick Institute in the UK and Shanghai Jiao Tong University in China.
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