The discovery disproves a widely accepted theory that reactive oxygen species (ROS) molecules fight infection but perpetuate inflammation.
“Our research suggests that ROS can be good for you even in inflammatory diseases like lupus,” said Jacob, director of the USC Lupus Genetic Group and principal investigator of the study. “This was not something we could have foreseen due to the scientific dogma.”
The study’s results were detailed in the Dec. 26 online edition of the Proceedings of the National Academy of Sciences.
Systemic lupus erythematosus (SLE, or lupus) is a long-term autoimmune disease that triggers inflammatory damage throughout the body, including the skin, joints, lungs, cardiovascular structures, nervous system and kidneys. There is no cure, and the underlying cause is not fully understood.
Jacob’s team used a proprietary methodology it developed, called Function2Gene, to search for genes associated with lupus. The method, which is available free of charge to scientists studying other complex diseases, targets fewer genes, resulting in a quicker and more cost-effective search.
The researchers then used computer modeling to hypothesize the functional consequences of the mutations identified in the gene. Finally, they tested their hypotheses in a live biological system, showing that the mutation decreases certain protein-to-protein interactions and ROS production. This discovery suggests that ROS may have a more nuanced regulatory function in the immune system than previously thought and may play a role in the predisposition to lupus.
The presence of the gene mutation could be used as diagnostic, Jacob said. The discovery also could lead to drug therapies that manipulate ROS levels, but more research into ROS biology is necessary, Jacob added.
Funding for the study came from the National Institutes of Health and the Alliance for Lupus Research.