March 9, 2011 -- Researchers think they may have discovered the mechanism that drives the body’s attack on its own cells and tissues in the autoimmune disease lupus.
Two new studies published in the journal Science Translational Medicine point to a cycle of cell death and chronic inflammation involving blood cells called neutrophils, versatile soldiers of the immune system that race to the site of infection to destroy invaders, as a key engine in the disease.
The discoveries come during a week when the FDA is expected to announce its decision on the biologic drug Benlysta, which could be the first drug approved to treat lupus in nearly 50 years.
According to the Lupus Foundation of America, lupus affects about 1.5 million Americans, many of them younger women.
The disease can affect many different parts of the body, including the skin, joints, lungs, heart, blood, and kidneys, which often makes it a challenge for doctors to diagnose.
One of the hallmarks of lupus is that patients make antibodies to their own DNA, called anti-nuclear antibodies, or ANAs. Blood tests for ANAs are sometimes helpful as an initial step in diagnosing lupus.
Researchers had long wondered how that happens since DNA was thought to be protected inside cells. Then, in 2004, a team of researchers discovered that neutrophils can die in an explosive way, shooting strings of cellular material studded with proteins and bits of nuclear DNA out like webs to entangle harmful bacteria, viruses, or fungi.
A Body Tangled by NETs
These neutrophil extracellular traps, or NETs, get slung outside the cell.
“They’re called NETs because they really look like a net, like a spider web,” says study researcher Michel Gilliet, MD, a dermatologist at University Hospital Lausanne, in Switzerland. The cells, he says, “shoot them out.”
In healthy people, once these NETs enter the liquid space between cells, the bits of nuclear DNA degrade quickly and probably don’t cause any problems, but Gilliet and his team found that patients with lupus have antimicrobial proteins called LL37 and HNP that appear to protect these bits of DNA from being broken down by the body.