photo: Chaim O. Jacob, M.D., Ph.D.
An international team of researchers led by
Chaim O. Jacob,
M.D., Ph.D., associate professor of medicine and microbiology &
immunology at the
Keck School of
Medicine of the
University of
Southern California,
has identified a gene mutation involved in causing lupus, a chronic
inflammatory disease that affects the skin, joints and organs.
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 are 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 they developed, called
Function2Gene,
to search for genes associated with lupus. Their 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 play a role in the predisposition to lupus.
The presence of the gene mutation could be used as diagnostic, Jacob
said. The discovery could also 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.