Scientists at the Australian National University have discovered that certain rare genetic mutations are a “major cause” of lupus, an occasionally fatal autoimmune disease that involves the immune system attacking the body's organs and tissues.
Lupus, which affects 1.5 million Americans and 5 million people worldwide, currently has no cure and its exact cause has always been hazy. It’s thought to be influenced by a combination of genetics, hormones, and environmental triggers such as sunlight. The autoimmune response may even be triggered by a gut bacterium called Enterococcus gallinarum.
With current treatments, lupus is rarely deadly, but it comes with a whole host of unpleasant symptoms. These range from tiredness and pain to a characteristic butterfly-shaped rash across the cheeks and nose, and even inflammation of vital organs such as the kidneys, lungs, and brain.
The idea that genes contribute to lupus is nothing new; the disease is known to run in families, but in a complex pattern that can’t be explained by simple Mendelian genetics.
"We have shown for the first time how rare gene variants that occur in less than 1 percent of the population cause lupus and how these variants drive the disease in the body," said Dr Simon Jiang, lead author of the new Nature Communications study, in a statement.
"Until now, it was thought that these rare variants played a negligible role in human autoimmunity and related autoimmune diseases.”
The researchers looked at the genetic makeup of 69 people with lupus and 97 healthy elderly individuals. They also looked at another group of 64 lupus patients to replicate their findings. They found that the majority of lupus patients have rare genetic variants in certain lupus-associated genes. The rare variants identified by the team were found to have negative effects on protein function, leading to increased T1 IFN protein activity in the immune system’s B cells. The variants were also found to increase levels of malfunctioning B cells in mice.
Most people with lupus have this excessive T1 IFN activity, which impairs B cells’ ability to function properly. These immune cells produce antibodies to fight off infection, but when they’re not working as they should, they get confused between invading bacteria and viruses and the body’s own cells, wrongfully attacking the latter.
Dr Jiang notes that the new findings could help to advance how lupus is treated, saying, “There is huge potential for targeted treatment"
"I've already started treating people who have these rare gene mutations with targeted therapies instead of bombarding their immune system with non-specific treatments that have lots of side effects – which is the current mainstay of therapy," he added. "And because the genes we have worked on are linked to other autoimmune diseases, our discovery could also be applied to conditions like rheumatoid arthritis and type 1 diabetes.”
The researchers also hope awareness of these rare genetic variants could help doctors diagnose lupus more swiftly. The condition is notably tricky to diagnose and can look very similar to other diseases, but analyzing a patient’s genetic information could cut the time it takes to make crucial these diagnoses.