CCP Antibodies in RA

Cyclic citrillinated peptide (CCP) antibodies are seen in rheumatoid arthritis. Tests for CCP antibodies help differentiate RA from other systemic rheumatic disorders

Antibodies to cyclic citrullinated peptide (CCP antibodies) are seen exclusively in patients with rheumatoid arthritis. These autoantibodies target a form of arginine known as citrulline and are seen in the early stages of progressive rheumatoid arthritis (RA). However, sensitive testing methods for these autoantibodies weren't available until 2000. And early tests for CCP showed specificity but lacked sensitivity. However, with the recent development of third generation enzyme linked immunosorbent assays (ELISA tests) for CCP (CCP3 antibody tests), cyclic citrilline peptide antibodies are considered the most sensitive markers for rheumatoid arthritis.

Unlike rheumatoid factor, which occurs in a number of different rheumatologic and autoimmune conditions as well as hepatitis C, cyclic citrullinated peptide antibodies using third generation tests are 74 percent sensitive for patients with rheumatoid arthritis. This offers a 5 percent improvement in sensitivity over earlier second generation tests. The third generation CCP3 antibody test gives rheumatologists the ability to diagnose rheumatoid arthritis earlier, allowing for earlier treatment intervention.

Rheumatoid arthritis is the most commonly occurring system autoimmune disease in the United States. However, it is often not diagnosed until permanent rheumatic changes have occurred. Confusion occurs because of the many different autoimmune diseases cause similar rheumatic symptoms, including systemic lupus erythematosus, mixed connective tissue disease, systemic Sjogren's disease, polymyositis, and systemic sclerosis. Further complicating diagnosis, most of these disorders cause similar immunological profiles (positive autoantibody test results), and test results change, with certain antibodies only showing up during disease flares.

Thirty years ago, researchers discovered that each of the systemic rheumatic diseases was associated with specific antinuclear antibodies (ANA). In particular, antibodies to chromatin and dsDNA are primarily seen in systemic lupus erythematosus (SLE) and antibodies to Smith (Sm) were specific markers for SLE. However, researchers were unable to find an antibody or marker specifically seen in rheumatoid arthritis. As mentioned, rheumatoid factor is seen in a number of different conditions.

Rheumatoid arthritis is clinically characterized by bilaterally symmetrical polyarthritis, that is, both sides of the body are affected equally. Three or more joints are typically affected and morning stiffness lasting more than one hour is seen. Some patients with RA have a mild, manageable disease, but most patients progress to an erosive form of arthritis in which joints are destroyed.

Besides having positive test results for rheumatoid factor, patients with RA have increased erythrocyte sedimentation rates, elevated levels of C-reactive protein (CRP), and joint erosions demonstrated on imaging tests. Because these characteristics can occur in the other systemic rheumatic disorders, the addition of CCP antibodies to the testing profile is a welcome addition. The presence of CCP antibodies is also associated with progression to more erosive disease. In some patients, CCP antibodies may be detected before symptoms of RA appear and before rheumatoid factor is seen. The ability to diagnose patients with RA who have only vague symptoms provides a treatment advantage.

Treatment for RA varies depending on the patient and can be used to alleviated pain and prevent disease progression. Traditional treatment strategies consisted of non-steroidal anti-inflammatory medications and later progressing to corticosteroids and other second-line agents such as methotrexate. Today, medications that inhibit immune system chemicals known as cytokines, such as tumor necrosis factor alpha, which promote inflammation, are used early in the disease course to prevent disease progression.

Resources:

Vossenaar ER and Van Venrooj WJL, Anti-CCP antibodies, a highly specific marker for early rheumatoid arthritis. Clin Applied Immunol Rev 4:239-262, 2004.

Saraux A et alL Value of antibodies to citrulline-containing peptides for diagnosing early arthritis, Journal of Rheumatology 30: 2535-2539; 2003.