Together, these proteins and DNA can trigger another type of immune cell, a kind of chemical factory called a plasmacytoid dendritic cell, which pumps out proteins that stoke the immune response.
One of those proteins, called type 1 interferon, is often present in high amounts in patients that have lupus, which has largely been another mystery of the disease.
Type 1 interferon, it turns out, triggers neutrophils to release more NETs, setting up an apparently self-perpetuating disease process.
“What this suggests is that there is a vicious cycle between the production of interferon, the way the neurtrophils die and the increase in the production of auto-antibodies, so this is a very, very efficient pathogenic loop that amplifies itself,” says study researcher Virginia Pascual, MD, an instructor of medicine at Baylor Institute of Immunology Research in Dallas.
Better Diagnosis and Treatments
Gilliet and his team are already testing the blood of lupus patients to see if one of these proteins may turn out to be a more specific marker for the disease, and thus useful in diagnosis.
That’s important because right now, doctors have to rely on a set of 11 criteria, which can overlap with many other diseases, to try to make a diagnosis.
“It is one of the most complex clinical diagnoses,” says Pascual, who is also a practicing pediatric rheumatologist.
“It might lead to better diagnostic tests, but we don’t know that yet,” Pascual says. Other experts say the discoveries will most certainly lead to new drug targets.
“It really provides a model for understanding why interferon is released, and that’s important because the more we understand why this very inflammatory cytokine is released, the more we can think about therapeutic options to block its production,” says Joseph E. Craft, MD, a rheumatologist and immunologist at Yale University in New Haven, Conn., who wrote a perspective article on the discoveries.
“That’s important because there are no really good therapies for patients with severe lupus,” he says.