Research could help stop lupus flares before they start

A new discovery from scientists at OMRF could be used by physicians to predict and prevent lupus flares.

Lupus is a multifaceted autoimmune disease in which the body’s immune system is unbalanced, which can lead to disease “flares” of inflammation, damaging tissue and organs.  The Lupus Foundation of America estimates 1.5 million Americans have the disease, which predominantly strikes women.

Patients are often not aware when a disease flare is about to occur. This delays treatment and allows inflammation to persist, putting patients at risk for organ damage.

“We’re often reacting to a bad situation in the clinic, rather than preventing the next one,” said Judith James, M.D., Ph.D., head of OMRF’s Arthritis and Clinical Immunology Research Program. “With this research, we hope we can identify the patients at the highest risk of flare and intervene earlier.”

In a new paper which will be published in the July issue of the journal Arthritis & Rheumatology, James and OMRF scientist Melissa Munroe, M.D., Ph.D., describe how a study of patients receiving an influenza vaccine led to a method that might predict flares in a clinical setting.

Lupus patients were evaluated just before receiving an influenza vaccine, and then tracked at 2, 6 and 12 weeks after receiving the shot.

“The initial study was to determine if the immune system of lupus patients could create antibodies to the influenza vaccine,” said Munroe. “Fortunately, the study design and the generosity of the patients allowed us to also gather this important information about lupus and what makes it flare.”

Researchers also monitored if the patients had a flare in the weeks after receiving the vaccine and looked at blood samples leading up to the attack.

“We were able to compare their immune system numbers to a baseline to identify potential indicators for inflammation,” said James, who holds the Lou C. Kerr Endowed Chair in Biomedical Research at OMRF.

For those with lupus, the immune system is like a teeter-totter, said Munroe. It’s almost always out of balance, with inflammation winning over regulation.

The study evaluated 52 mediators—molecules that increase or decrease the chance of a lupus flare by driving or suppressing inflammation, she said. These can be used to “score” patients to predict who might need a pre-flare intervention as many as three months in advance.

They have filed for a provisional patent for the system.

“Even if they aren’t feeling too bad, patients’ immune systems are warning us that a flare is coming,” James said. “If we know they’re not going to flare, we can avoid giving them a lot of unnecessary and potentially toxic drugs.”

The discovery will help physicians move closer to tailored therapies for patients, but it could also have a potential benefit for clinical trials, she said. One challenge in testing new medications for lupus is discerning if a lack of disease activity is due to a drug’s effects or other factors.

In the next step, researchers will seek to use the data to group patients into smaller sets in order to better treat their specific disease, James said.

“I’ve had two lupus patients sitting together discussing their symptoms, and they don’t realize they have the same disease,” she said. “This could allow doctors to define patients from a molecular standpoint and really get at precisely what’s happening in their disease process.”

This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Allergy and Infectious Diseases with co-funding by the Office of Research on Women’s Health, and the National Institute of General Medicinal Sciences of the National Institutes of Health under award numbers P30AR053483, U19AI082714, U01AI101934, P30GM103510, S10RR026735, and HHSN266200500026C. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.