Rheumatoid arthritis drugs treat inflammation, but not the underlying autoimmunity.
While rheumatoid arthritis (RA) treatments can keep inflammation at bay, an immunologic defect can trigger inflammation and cause a relapse. Researchers from the New York University (NYU) Langone Medical Center in New York City looked at the defective molecules produced by the immune system’s B cells, called autoantibodies.
Gregg Silverman, MD, professor in the departments of Medicine and Pathology at NYU Langone, and colleagues studied the underlying autoimmunity in these patients and why immune responses act against the body’s own healthy cells and tissues. Their research suggests clinical trials examining RA drugs should focus on not just relieving inflammation, but getting rid of the B cells which produce the antibodies which cause the inflammation.
Initial RA treatment typically starts with the inflammation blocker and follow by drugs which block the molecule tumor necrosis factor (TNF). These medications can help control inflammation and swellings, and even allow patients to go into remission. Silverman said that the decrease in inflammation doesn’t necessary reflect RA disease activity. Stopping the drugs, however, could cause patients’ symptoms to flare up sooner.
“We have developed a test for measuring the underlying autoimmunity in RA patients that should be used to evaluate new treatment regimens,” said Silverman, senior author of the study.
The researchers looked at “memory” B cells, which remember initial errant encounters that determined the body’s own proteins were foreign. These memory B cells produce molecules known as anti-citrullinated protein antibodies (ACPAs) in patients with RA, which is what physicians look for in the blood to diagnose people with the condition.
The NYU Langone team developed assays that are able to detect difference antibodies associated with RA. The researchers established a cell culture system in order to stimulate memory B cells, then tested the sensitive assays. When tested on people with RA and healthy controls, those with disease had high levels of APCA-secreting memory B cells. However, around 80% of people with RA actually have those antibodies, so those high levels weren’t found in patients without them.
Looking at a subgroup of patients with RA who were in remission from methotrexate or a TNF inhibitor, it became apparent that the APCA levels were directly proportional to the recirculating memory B cells in the blood stream. This meant that the treatments do not actually impact the underlying autoimmunity of the disease.
“This new tool may show that agents that target other molecules or cells have advantages that were previously not considered now that we can better measure those effects,” explained Silverman, who is also co-director of the Musculoskeletal Center of Excellence at NYU Langone.
He said that the next step of this research is to use the test in long-term trials evaluating RA drugs. Until enough evidence persuades otherwise, medications continue to focus on inflammation and not the underlying mechanism.
The study, “Disease associated anti-citrullinated protein memory B cells in rheumatoid arthritis persist in clinical remission,” was published in Arthritis & Rheumatology. The news release was provided by NYU Langone Medical Center.