Genetic mutation is potential cause of lupus

by Trinity Cardinal

Lauren Dempsey, MS in Biomedicine and Law, RN, FISM News 


About 5 million people globally are affected by lupus, an autoimmune disease where the immune system attacks almost every organ in the body. This results in a wide range of symptoms from joint pain, rashes, fatigue, muscle pain, hair loss, memory problems, and light sensitivity. In severe cases, the symptoms can be debilitating and fatal. 

There is no cure for lupus and treatment includes symptom management by taking immune suppressors, which inhibit the ability of the immune system and prevent it from attacking itself. New research on the cause of lupus may help researchers better understand the disease and discover more effective treatments for patients.

Researchers at the Centre for Personalized Immunology at the Australian National University published the results of their study in Nature earlier this week. The report details how they conducted whole-genome sequencing on the DNA of  Gabriela, a Spanish girl who was diagnosed with severe lupus at 7 years old. Usually, onset at such an early age suggests a genetic component. 

Genetic analysis found a single point mutation in the TLR7 (toll-like receptor 7) gene, which is programmed to help the immune system protect against viral infections. In Gabriela’s case, the TLR7 gene mutation enhances binding between proteins and guanosine, which causes the immune system to become overly sensitive and attack healthy cells. Scientists were able to identify other cases of severe lupus with this gene mutation through referrals from the United States and the China Australia Centre of Personalised Immunology (CACPI) at Shanghai Renji Hospital.

To verify their suspicions, the researchers used a technology called CRISPR gene-editing to modify the DNA of mice. The mice did develop lupus, providing evidence that the TLR7 mutation was the cause. The strain of mice created was named  ‘Kika’ by Gabriela. The results help scientists and clinicians understand one cause of lupus. 

It also might help to explain why women are ten times more likely to have lupus than men. The TLR7 gene is found on the X chromosomes, females have two copies of the gene, while males only have one. “This means females with an overactive TLR7 gene can have two functioning copies, potentially doubling the harm,” professor and co-author of the study Carola Vinuesa said. 

 This is only one potential cause of lupus, experts believe that hormonal and environmental triggers can also be factors. Not every patient with lupus will have a genetic mutation, however, study co-author Professor Nan Shen, a co-director of the China Australia Centre of Personalized Immunology explains that many of these patients do have TLR7 genes that are overactive, suggesting some sort of correlation or “causal link” between the gene and the disease. 

Researchers are hopeful that this will lead to the discovery of better treatment for lupus patients. Vinuesa says “It has been a huge challenge to find effective treatments for lupus, and the immune-suppressors currently being used can have serious side effects and leave patients more susceptible to infection. There has only been a single new treatment approved by the FDA in about the last 60 years.”