Researchers looking for blood-based biomarkers that could predict rheumatoid arthritis flare-ups have unexpectedly discovered a never-before-seen type of cell. Dubbed PRIME cells, they were seen to accumulate in the bloodstream seven days before a flare, but strangely disappear during the flare.
The novel research began by recruiting four rheumatoid arthritis sufferers, and tasking them with collecting weekly finger-prick blood samples for up to four years. Alongside the blood samples, the cohort tracked personal symptoms and flare-ups so the investigators could ascertain any correlation between blood markers and disease activity.
Studying RNA expression in the blood samples, the researchers noticed something strange consistently appear in all subjects about seven days before they experienced a flare-up. A mysterious cell, with an RNA profile not seen in blood or immune cells. What the researchers were seeing more resembled synovial fibroblasts, a type of cell usually found in joints and not freely circulating in the bloodstream.
“That got us thinking there was something fishy going on," says co-author on the study, Dana Orange. “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.”
The researchers named the newly discovered cells PRIME cells, short for PRe-Inflammation MEsenchymal cells. And now they knew what to look for they tested 19 more rheumatoid arthritis patients to confirm these PRIME cells do seem to appear in the days leading up to an acute flare-up.
But even more curiously, these PRIME cells disappear from the bloodstream once a flare-up begins. This observation has led the researchers to hypothesize the PRIME cells may migrate from the blood into the membranes of joints and be the active cause of rheumatoid arthritis flare-ups.
It is still early days for the research, and the presence of PRIME cells as a precursor to a rheumatoid arthritis flare-up needs to be verified in more patients. However, the possible implications of this new discovery are significant.
Robert Darnell, whose lab led the new research, hopes the discovery could lead to a simple testing device to help arthritis sufferers better predict an oncoming flare-up. More importantly, further study into the molecular characteristics of these PRIME cells may lead to new treatments to stop flare-ups before they begin.
“PRIME cells are one thing you might want to target to arrest the flare before it happens,” says Darnell. “That’s the ideal of medical science – to know enough about a disease that you can put your finger on what’s about to make someone sick. If these cells are the antecedents to joint sickness, they become a potential target for new drugs.”
The new study was published in The New England Journal of Medicine.
Source: Howard Hughes Medical Institute, Rockefeller University