OKLAHOMA CITY — Oklahoma Medical Research Foundation scientists have deepened their understanding of how the immune system changes before lupus patients experience a flare of their disease.

The findings will help push clinicians closer to personalized medicine for lupus sufferers.

Lupus is caused when the immune system becomes unbalanced, leading to the development of autoantibodies and chronic inflammation that damage the body’s organs and tissues. Lupus sufferers have periods of flares and remission with organs typically affected including the skin, kidneys, lungs and joints, as well as the cardiovascular system.

“One of the big challenges with lupus is that sometimes the disease isn’t so bad, and then other times you have these major life-threatening or organ-threatening flares,” said OMRF Vice President of Clinical Affairs Judith James, M.D., Ph.D. “We know that about 80 percent of lupus patients have disease that waxes and wanes, but we’ve never fully understood what changed in the immune system to drive a flare.”

James’ team along with OMRF scientists Joel Guthridge, Ph.D., and Joan Merrill, M.D., has worked for years to identify cell markers of flares, and a new paper published in the journal Scientific Reports shows OMRF has taken a significant step toward achieving this goal.

Building off a clinical trial called BOLD, or Biomarkers of Lupus Disease, OMRF researchers used machine learning and artificial intelligence tools to look closely at immune cells and other clinical factors to identify individuals who were at the highest risk of flares. “Not surprisingly,” James said, “we found that lupus patients flare in different ways.”

Lupus flares can occur in different parts of the immune system. By understanding which markers to look for in advance, clinicians will have the tools to predict and treat specific pathways most likely to flare on a case-by-case basis.

“If we can identify those about to experience a flare, we can use milder medications that have fewer side effects earlier,” said James, who holds the Lou C. Kerr Chair in Biomedical Research at OMRF. “It would also allow us to be proactive and intervene with drugs before organ damage begins.”

That’s important, she said, because doctors already have therapies approved for other diseases that zero in on these specific cell types. “If we knew a patient was going to flare and had a certain cell type, they might benefit from taking an existing medication. This gets us closer to personalized medicine so we can know what medicine to use in whom and when.”

By using medicines already approved for other conditions, patients can benefit much sooner, rather than waiting many years for new medications to be developed and approved.

Funding for this work was provided by the National Institute of Allergy and Infectious Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and the National Institute of General Medical Sciences.

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