A team of researchers funded in part by the NIH’s National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) has identified a pattern of biological molecules in the blood of people with systemic lupus erythematosus (SLE) that signals the onset of a disease flare. The molecular pattern they have found may help doctors to predict oncoming flares and enable them to treat patients aggressively before symptoms become full-blown. The study appeared in the journal Arthritis and Rheumatology.
SLE, or lupus, is an autoimmune disease in which the immune system mistakenly attacks its own tissues and organs, causing inflammation. The symptoms vary, but the most common ones are sore, swollen joints, muscle aches and fatigue. Over time, SLE can damage the body’s organs and cause serious problems like kidney disease or cardiovascular disease. There is no cure for the disease, but non-steroidal anti-inflammatories, steroids and other immune suppressants are used to control the symptoms.
SLE is a chronic condition, with periods of remission alternating with debilitating relapses. If doctors could recognize the onset of relapses using biological markers in a patient’s blood, they could treat them promptly and possibly quell them before they produce painful symptoms or organ damage.
"A simple blood test for predicting flares would fill a major gap in our ability to treat people with SLE," said Judith James, M.D., Ph.D., of the Oklahoma Medical Research Foundation and senior author of the study. "It would represent an important first step toward lowering the frequency of these troubling episodes."
To see if they could identify biomarkers for SLE flares before symptoms occurred, Dr. James’ team analyzed blood samples from 28 SLE patients in a pre-flare state—these patients developed a flare 6-12 weeks after their blood was drawn. They compared these with blood samples from 28 SLE patients whose disease remained stable in the weeks following the blood draw.
The analysis revealed significant differences in the levels of 27 biologic molecules. A number of inflammatory molecules were elevated in the pre-flare group, while molecules that help control inflammation were higher in the control group. The researchers observed a similar pattern in a subset of 13 patients when they compared blood samples from the same individual in a pre-flare state and a stable clinical period.
The scientists next used the data to develop a system for scoring the risk of a disease flare based on the balance of inflammatory and regulatory molecules in a patient’s blood. If validated, the scoring system may help doctors optimize the treatment of each individual patient by ensuring that therapies are administered only when needed to avert a disease flare.
"Not only will these biomarkers help us assess the risk of impending flares in SLE patients, but they may also point to the underlying mechanisms that incite them," said Dr. James. "These biomarkers could help us better understand how flares arise at the biochemical level, and possibly lead to the development of targeted medicines to combat them."
This research was supported by the NIH’s NIAMS (grant P30-AR053483), National Institute of Allergy and Infectious Diseases (grants U19-AI082714, U01-AI101934 and contract award HHSN266200500026C), Office of Research on Women’s Health, and National Institute of General Medical Sciences (grants P30-GM103510 and S10-RR026735).
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Munroe ME, Vista ES, Guthridge JM, Thompson LF, Merrill JT, James JA. Proinflammatory adaptive cytokine and shed tumor necrosis factor receptor levels are elevated preceding systemic lupus erythematosus disease flare. Arthritis Rheumatol. 2014 Jul;66(7):1888-99. doi: 10.1002/art.38573. PMID: 24578190
The mission of the NIAMS, a part of the U.S. Department of Health and Human Services' National Institutes of Health, is to support research into the causes, treatment and prevention of arthritis and musculoskeletal and skin diseases; the training of basic and clinical scientists to carry out this research; and the dissemination of information on research progress in these diseases. For more information about the NIAMS, call the information clearinghouse at (301) 495-4484 or (877) 22-NIAMS (free call) or visit the NIAMS website at https://www.niams.nih.gov.