Although most people with RA test positive for rheumatoid factor, many people who do not have RA also test positive for rheumatoid factor, limiting the diagnostic value of this test. It has been found that testing for antibodies against cyclic citrullinated peptide, or anti-CCP, is much more specific for identifying people with RA. Furthermore, anti-CCP antibodies may be present for years before disease symptoms are apparent, making this antibody a potential predictor of who will develop disease. Although the relationship between anti-CCP antibodies and RA has been known for a few years, research studies released in 2006 have increased our understanding of the role and importance of anti-CCP proteins.

In April 2006, a multicenter team of scientists released results in The Journal of Clinical Investigation about the role of anti-CCP antibodies in the onset and continuation of RA. They found that antibodies against citrullinated proteins (proteins that have a citrulline molecule attached) do indeed contribute to the development of RA. The article’s senior author, V. Michael Holers, MD, stated, “knowing [this] may allow for the development of targeted therapeutics that inhibit these antibodies or their development. Such therapeutic approaches may reduce severity in patients with active disease or perhaps even prevent the onset of clinically significant arthritis in susceptible individuals.”

A Swedish group of scientists found an important association between anti-CCP antibodies, the shared epitope genetic marker, smoking and RA – providing an important clue about the way genetics and the environment may interact to trigger the onset of RA (Arthritis & Rheumatism, January 2006).

They found that the presence of the shared epitope increases the risk of developing RA only in the subgroup of people who are positive for anti-CCP antibodies. They also found that smokers with two copies of the shared epitope genes had a 21-fold greater risk of developing RA compared with nonsmokers who do not carry the genes. Importantly, they were able to determine what happens in the body that ties together the environmental trigger (smoking) with the genetic background (presence of the shared epitope). They found that an immune reaction to citrullinated proteins occurs almost exclusively in individuals with the shared epitope genes who also smoke. The lead study author Lars Klareskog, MD, PhD, notes in the article, “These findings may provide new opportunities to both predict and understand the onset of RA and to interfere with RA-inducing events before clinical symptoms are apparent.”