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Researchers Discover a New Type of Cells That May Predict Flares in Rheumatoid Arthritis

A newly discovered type of cell present in the blood may predict episodes of joint inflammation known as flares in people with rheumatoid arthritis a week or two before the episodes occur, according to a study by researchers at Rockefeller University/Hospital for Special Surgery (HSS), Brigham and Women’s Hospital and Princeton University. The discovery may represent a new treatment target for warding off flares in advance.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes painful joint inflammation. The immune system mistakes body tissue as foreign and attacks it. Symptoms can change dramatically, with stable periods interrupted by flares that can cause irreversible destruction to cartilage and bone over time. Current treatments focus on treating inflammation and slowing disease progression by reducing immune cell activity.

“Patients with RA experience unpredictable, dynamic flares that make it difficult to perform activities of daily living,” says Dana Orange, MD, assistant professor of clinical investigation at Rockefeller University and assistant attending rheumatologist at HSS. “There is a real need to understand what happens in the body as flares arise.”

Dr. Orange, lead author on the study published July 15 in the New England Journal of Medicine, and colleagues, designed a new way to study changes that occur in the body when a flare arises. They developed a new lab test capable of analyzing three drops of “finger-stick” blood per sample collected by patients at home. Study participants mailed in their blood samples weekly along with completed surveys on their symptoms.

The researchers obtained samples from 364 time points from eight flares over four years from the first patient. They also received samples from 235 time points from flares from three additional patients. Dr. Orange saw patients in monthly clinic visits at the Rockefeller University Hospital with extra visits as required during flares. The visits included standard blood tests and disease activity assessments.

Next, the researchers performed RNA sequencing on the blood samples to look for differences in gene expression over time leading up to flares. They discovered a new type of cell in circulating blood that they named PRIME cells (PRe-Inflammatory MEsenchymal) cells. Mesenchymal cells are capable of becoming tissue and cartilage.

The number of PRIME cells increased in circulating blood before flares occurred and decreased during flares in all four patients. By analyzing cell sequencing data collected previously by the Accelerating Medicines Partnership (AMP) in Rheumatoid Arthritis and Lupus Network (AMP RA/SLE consortium), the researchers found that PRIME cells shared similar features with sublining fibroblasts, cells that are found in joints that are known to become aggressive in RA.

Finally, the investigators confirmed the presence of PRIME cells in 19 additional patients with RA. Dr. Orange and colleagues also observed that immune cells called B cells were activated in blood before flares occurred. “We think that PRIME cells may become activated by B cells in the weeks before a flare and then migrate from the blood into joints during a flare,” says Dr. Orange. “But more research is required before a causal relationship can be established between B cells and PRIME cells. Our work in this area is ongoing.”

“Overall, we think that PRIME cells may act as gatekeepers and play a critical role in RA disease processes,” says Dr. Orange. “If that’s true, it opens up a whole new field of research that may one day lead to new treatments that can shut down flares before they happen.”

The study was supported by funding provided by the National Institutes of Health, the Robertson Foundation, the Bernard and Irene Schwartz Foundation, the National Center for Advancing Translational Sciences, the Simons Foundation and the Rheumatology Research Foundation of the American College of Rheumatology.

About HSS

HSS is the world’s leading academic medical center focused on musculoskeletal health. At its core is Hospital for Special Surgery, nationally ranked No. 1 in orthopedics (for the 14th consecutive year), No. 2 in rheumatology by U.S. News & World Report (2023-2024), and the best pediatric orthopedic hospital in NY, NJ and CT by U.S. News & World Report “Best Children’s Hospitals” list (2023-2024). In a survey of medical professionals in more than 20 countries by Newsweek, HSS is ranked world #1 in orthopedics for a fourth consecutive year (2023). Founded in 1863, the Hospital has the lowest readmission rates in the nation for orthopedics, and among the lowest infection and complication rates. HSS was the first in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center five consecutive times. An affiliate of Weill Cornell Medical College, HSS has a main campus in New York City and facilities in New Jersey, Connecticut and in the Long Island and Westchester County regions of New York State, as well as in Florida. In addition to patient care, HSS leads the field in research, innovation and education. The HSS Research Institute comprises 20 laboratories and 300 staff members focused on leading the advancement of musculoskeletal health through prevention of degeneration, tissue repair and tissue regeneration. In addition, more than 200 HSS clinical investigators are working to improve patient outcomes through better ways to prevent, diagnose, and treat orthopedic, rheumatic and musculoskeletal diseases. The HSS Innovation Institute works to realize the potential of new drugs, therapeutics and devices. The HSS Education Institute is a trusted leader in advancing musculoskeletal knowledge and research for physicians, nurses, allied health professionals, academic trainees, and consumers in more than 165 countries. The institution is collaborating with medical centers and other organizations to advance the quality and value of musculoskeletal care and to make world-class HSS care more widely accessible nationally and internationally.