Researchers have found that structures present in the joint linings of some patients with rheumatoid arthritis are able to produce anti citrullinated protein antibodies (ACPA) that may be responsible for joint damage.
10 January 2009
In a paper published in the January issue of the Americal journal PLoS Medicine, Professor Costantino Pitzalis, Head of Centre for Experimental Medicine and Rheumatology at Barts and the London School of Medicine and Dentistry, and colleagues at King’s College London, report the first direct evidence that ectopic lymphoid structures found within synovial tissue, can produce the enzyme activation-induced cytidine deaminase (AID); this enzyme can in turn trigger an immune system mechanism, producing anti-CCP antibodies which are associated with rheumatoid arthritis.
More than 350,000 people in the UK have rheumatoid arthritis, an autoimmune condition that affects the joints. Normally, the immune system provides protection against infection by responding to foreign antigens while ignoring self-antigens present in the body’s own tissues. In autoimmune diseases, this ability to discriminate between self and non-self fails for unknown reasons and the immune system begins to attack the body’s tissues. In rheumatoid arthritis, the lining of the joints (the synovium) becomes inflamed and thickened, and chemicals are released that damage all the tissues in the joint. Eventually, the joint may become so scarred that movement is no longer possible.
The researchers collected synovial tissue from 55 patients with rheumatoid arthritis and found that in all cases the ectopic structures in the synovium expressed the AID enzyme. They also found that the structures were surrounded by mature B cells, which continued to survive and produce antibodies, even in an environment lacking new incoming immune cells.
The results go some way to explaining why drugs that clear B cells from the bloodstream do not always produce a marked clinical improvement in rheumatoid arthritis patients; and suggest there is a need to target these ectopic structures within the diseased tissue.
They also suggest that the enzyme AID may provide a new target for the development of drugs to treat rheumatoid arthritis.
For media information, contact:Joel Winston