RA Treatment Decreases Joint Inflammation

Glucocorticoid therapy appears to help reduce the amount of citrullination in the joints of rheumatoid arthritis (RA) patients, researchers have found.

Individuals who suffer from RA have increased levels of protein citrullination (CP) in their joints, which apparently contributes “to the perpetuation of chronic inflammation in the presence of specific autoimmunity,” write the researchers in their study’s abstract.

Led by Anca Catrina, MD, PhD, from the Karolinska Institute and University Hospital in Sweden, researchers from three countries—Sweden, America, and the Netherlands—conducted the study involving 39 patients.

Synovial biopsies were collected from 11 RA patients prior to and following eight weeks of treatment with 20 mg of methotrexate weekly; 15 RA patients prior to and two patients following an intra-articular glucocorticoid injection; five osteoarthritis patients; and eight healthy control participants.

From these biopsies, the researchers found that synovial CP was present almost exclusively in RA patients. They also found increased levels of the enzymes peptidylarginine deiminase (PAD) 2 and 4 in the RA patients.

Further, “both the level of CP and of PAD correlated with the extent of inflammation—the more CP and PAD the worse the inflammation,” according to a press release. “Treatment with methotrexate, an anti-rheumatic drug, used to treat RA, had no effect on the levels of CP or PAD.”

The joints of the RA patients who were treated with glucocorticoids but not methotrexate, however, expressed decreased levels of synovial citrullinated proteins and peptidylarginine deiminase enzymes, which were correlated with a decrease in inflammation. A single dose of glucocorticoids was found capable of reducing both the level of CP and PAD 4.

These effects were only observed in cells from the inflamed joints, as the researchers tested synovial fluid and blood from people with RA and found that only the cells from the synovial fluid reacted to the treatment with a decrease in CP and PAD2 or PAD4.

“Synovial citrullination and PAD expression is depended on local inflammation and targeted by glucocorticoids,” the researchers concluded in the abstract.

This study was published online today in a provisional PDF in Arthritis Research & Therapy.