Newly Discovered Blood Cells Predict Rheumatoid Arthritis Flareups

By Pat Anson, PNN Editor

A simple blood test could give an early warning to rheumatoid arthritis sufferers that their symptoms are about to get worse, according to a new study published in the New England Journal of Medicine.   

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the body’s own defenses attack joint tissues, causing pain, inflammation and bone erosion. The symptoms come in waves, with periods of remission interspersed with painful flareups.

Researchers at Rockefeller University have identified a new type of cell – called "PRIME cells" – that dramatically increase in the blood of RA patients a week before a disease flareup.

“If we can reliably identify these new cells in patients, we may be able to tell them ‘You’re about to have a flare,’ so they can prepare themselves,” says lead author Robert Darnell, MD, a neuroscientist at Rockefeller’s Howard Hughes Medical Institute. “This would make flares less disruptive and easier to manage.”

Over a four-year period, researchers analyzed hundreds of blood samples from four RA patients, who collected the blood at home using finger pricks and sent them to Darnell’s lab. Each participant also kept a record of their symptoms to identify when flares occurred.

National Institutes of Allergy and Infectious Diseases

Darnell and his colleagues looked for molecular changes in the blood prior to the onset of symptoms, and saw an increase in immune cells two weeks prior to a flare. That was not surprising, because the cells are known to attack the joints of RA patients.

But in samples collected one week before a flare, researchers saw an increase in cells that didn't match the genetic signature of any known type of blood or immune cell. The RNA signature of the cells resembled that of bone, cartilage or muscle cells – which are not typically found in blood.

“We were so surprised to see that the genes expressed right before a flare are normally active in the bone, muscle, and extracellular matrix -- strange pathways to find in blood cells,” said coauthor Dana Orange, MD, a rheumatologist at Rockefeller. “That really piqued our interest.”

Darnell's team named their discovery PRIME cells because they are "pre-inflammation mesenchymal" cells -- a type of stem cell that can develop into bone or cartilage. Notably, while PRIME cells accumulated in the blood before flares, they disappeared during them.

Researchers say PRIME cells have RNA profiles that are strikingly similar to synovial fibroblasts, which are found in the tissue lining of joints and are known to play a role in causing RA symptoms. In experiments on laboratory mice, fibroblasts that were removed from inflamed joints and transplanted into healthy mice caused them to become arthritic too.

Researchers are now recruiting RA patients for a larger study to confirm whether PRIME cells can predict a flare. If the cells do act as a precursor, it could lead to the development of drugs that target PRIME cells and stop flares before symptoms worsen.

“For doctors and patients, intervention before a flare up is always better than just treating symptoms,” says Darnell. “If these cells are the antecedents to joint sickness, they become a potential target for new drugs.”