A surprise mechanism uncovered in the development of lupus

October 25, 2012
A surprise mechanism uncovered in the development of lupus
Credit: Shutterstock

In a study with a surprising outcome, scientists at Yale School of Medicine have discovered that an enzyme complex known for promoting natural resistance to bacteria and fungi unexpectedly inhibits the development of lupus. The finding could pave the way for development of therapeutic interventions in this debilitating disease. The study appears online in the Oct. 24 issue of Science Translational Medicine.

(SLE) is an autoimmune disease in which the immune system attacks the body's healthy tissue rather than foreign pathogens, resulting in inflammation and damage to joints and . The etiology of lupus is not well understood, but the suspected cause is debris produced when cells die.

The Yale researchers focused on a key enzyme complex in this process known as NADPH oxidase, or Nox2, and evaluated its role in lupus pathogenesis.

Before this study, it was commonly thought that Nox2 might actively promote the development of lupus by facilitating the release of DNA from called in a process called NET ("neutrophil extracellular trap") generation. To test that hypothesis, the Yale team evaluated disease in lupus-prone mice that lacked the Nox2 protein. Contrary to expectations, the Nox2-deficient mice whose neutrophils failed to generate NETs not only still got lupus, but got a much worse form of the disease. Surprised by the finding, researchers realized that normal function of Nox2 inhibits the development of lupus, rather than promoting it.

They are now focusing their research on how Nox2 controls lupus. "Nox2 clearly has an important role in fighting infection and lupus is often triggered by infection. We suspect that Nox2 could be an important connection between response to infection and lupus flares," said lead author Mark Shlomchik, M.D., professor of laboratory medicine and immunobiology at Yale School of Medicine. "We now plan to explore the mechanism by which NADPH oxidase is exerting its effects. Doing so should provide additional insights into the cause of this disease."

The implication for human cases of lupus could be enormous. "We suspect that without NADPH oxidase, neutrophils may die in a way that inflames the immune system," Shlomchik explains. "This may help us develop therapies that promote NADPH oxidase function and thereby suppress disease."

Explore further: Study: Epstein Barr virus protects against autoimmune disease

Related Stories

Study: Epstein Barr virus protects against autoimmune disease

April 2, 2012

To the surprise of investigating researchers, an animal model of Epstein Barr virus protected lupus-prone mice against development of the autoimmune disease. Earlier work had suggested that EBV might promote the development ...

Recommended for you

Monkeys in Asia harbor virus from humans, other species

November 19, 2015

When it comes to spreading viruses, bats are thought to be among the worst. Now a new study of nearly 900 nonhuman primates in Bangladesh and Cambodia shows that macaques harbor more diverse astroviruses, which can cause ...

One-step test for hepatitis C virus infection developed

November 14, 2015

UC Irvine Health researchers have developed a cost-effective one-step test that screens, detects and confirms hepatitis C virus (HCV) infections. Dr. Ke-Qin Hu, director of hepatology services, will present findings at the ...

Computer model reveals deadly route of Ebola outbreak

November 10, 2015

Using a novel statistical model, a research team led by Columbia University's Mailman School of Public Health mapped the spread of the 2014-2015 Ebola outbreak in Sierra Leone, providing the most detailed picture to date ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.