Steroids prevent protein changes seen in the joints of people with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease where the body begins to attack the joints and organs of the body. Proteins within inflamed joints are often modified by citrullination, a process that converts the protein building block arginine into citrulline. These two amino acids have very different physical properties and consequently conversion can result in aberrant changes in the three-dimensional structure of an affected protein. New research published in BioMed Central's open access journal Arthritis Research & Therapy shows that glucocorticoid therapy can reduce the amount of citrullination and the amount of the enzyme peptidylargininedeiminase 4 (PAD4) responsible for citrullination in the joints of people with RA.

People with RA have excessive amounts of protein citrullination in their inflamed joints. It is thought that these proteins are involved in initiating and maintaining the joint inflammation seen in people with RA. Researchers from three countries, Sweden, America, and the Netherlands collaborated to look at the levels of citrullinated proteins in the joints of people with RA, and compared the before and after effect of current treatments – methotrexate and glucocorticoids.

As expected elevated levels of citrullinated proteins (CP) were found in the knees of people with RA, compared to the joints of the control group. The new research also discovered enhanced levels of the enzymes (PAD2 and 4), responsible for these aberrant proteins, in the biopsies of people with RA. Additionally both the level of CP and of PAD correlated with the extent of inflammation – the more CP and PAD the worse the inflammation.

Treatment with methotrexate, an anti rheumatic drug, used to treat RA, had no effect on the levels of CP or PAD. However a single injection of glucocorticoid was able to reduce both the level of protein citrullination and PAD4, and this was matched by a decrease in visible signs of inflammation.

The beneficial effect of glucocorticoids was limited to cells from the inflamed joints. A synthetic glucocortioid (DEX) was tested in on both synovial fluid and blood from people with RA, but only the cells from the synovial fluid responded with a decrease in CP and PAD2 or PAD4.

Dr Anca Catrina from the Karolinska Institute and University Hospital who led the research explained that future tailoring of RA management and the development of new treatments is dependent on a better knowledge of the disease. She said, "Our work has been able to establish for the first time that different treatments have different effects on protein citrullination, an important process in the progression of RA."

More information: Local administration of glucocorticoids decrease synovial citrullination in rheumatoid arthritis, Dimtrios Makrygiannakis, Shankar Revu, Marianne Engström, Erik afKlint, Anthony P Nicholas, Ger JM Pruijn and Anca I Catrina, Arthritis Research & Therapy (in press)

add to favorites email to friend print save as pdf

Related Stories

Latest rheumatoid arthritis drugs compared

Apr 17, 2008

Findings published today in the open access journal BMC Musculoskeletal Disorders shows that the latest class of drugs used to treat rheumatoid arthritis (RA) are better than standard anti-inflammatories.

Defect in A20 gene expression causes rheumatoid arthritis

Aug 16, 2011

Researchers from VIB (Flanders Institute for Biotechnology) and Ghent University have shown that a defective gene can contribute to the onset of rheumatoid arthritis, an often-crippling inflammation of the joints that afflicts ...

Recommended for you

Increased insulin resistance in rheumatoid arthritis

Dec 11, 2014

(HealthDay)—Patients with rheumatoid arthritis (RA) have elevated insulin resistance (IR), but this is not associated with increased atherosclerosis risk, according to a study published online Dec. 10 in ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.