A surprise mechanism uncovered in the development of lupus

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."

Related Stories

Rescue NET for lupus patients

May 03, 2010

Lupus is a disease where the immune system attacks healthy cells of the body. This leads to progressive damage of different tissues and organs. The classical characteristic of the disease is the so-called ...

Immune cell plays unexpected role in autoimmune disease

Dec 16, 2010

A new study provides fascinating insight into the underlying pathology associated with the autoimmune disease, systemic lupus erythematosus (SLE). The research, published by Cell Press in the December issue ...

Recommended for you

UN says Syria vaccine deaths was an NGO 'mistake'

8 hours ago

The recent deaths of Syrian children after receiving measles vaccinations was the result of a "mistake" by a non-governmental partner who mixed in a muscle relaxant meant for anesthesia, a spokesman for the U.N. secretary-general ...

First US child dies from enterovirus D68

9 hours ago

A child in the northeastern US state of Rhode Island has become the first to die from an ongoing outbreak of a respiratory virus, enterovirus D68, health officials said Wednesday.

US Ebola patient had contact with kids: governor

9 hours ago

A man who was diagnosed with Ebola in virus in Texas came in contact with young children, and experts are monitoring them for any signs of disease, governor Rick Perry said Wednesday.

UN worker dies of suspected Ebola in Liberia

9 hours ago

The United Nations mission in Liberia announced on Wednesday the first suspected victim among its employees of the deadly Ebola epidemic ravaging the impoverished west African nation.

User comments