Peptide (CCP) Anti-CCP

Rheumatoid Arthritis (RA) is a common, systemic autoimmune disease affecting 0.5- 1.0% of the adult population. RA is characterised by chronic inflammation of the synovium which can lead to progressive joint destruction and in many cases lead to disability and reduction of quality of life.1 It is generally accepted that early intervention is vital in preventing irreversible joint damage and it is therefore important to diagnose RA as early in the disease course as possible.2,3 The diagnosis of RA is primarily based on clinical, radiological and immunological features. The most frequent serological test is the measurement of rheumatoid factor (RF).4 Although the RF test has good sensitivity, it is not specific for RA, as it is often present in healthy individuals and patients with other rheumatic or inflammatory diseases, autoimmune diseases or chronic infections.5 For several years, it has been recognised that antibodies to anti-perinuclear factor (APF) and keratin (AKA) are highly specific for RA. It was subsequently reported that both these antibodies reacted with native filaggrin and now are referred to as anti-filaggrin antibodies (AFA).6,7,8 Recent evidence has shown that all these antibodies are directed to citrulline containing epitopes.9 Citrulline is a non-standard amino acid, as it is not incorporated into proteins during protein synthesis. It can however be generated via posttransitional modification of arginine residues by the enzyme peptidylarginine deiminase (PAD).10 In 1998, Schellekens and colleagues reported that autoantibodies reactive with linear synthetic peptides containing citrulline were highly specific for RA in an ELISA based assay.11 Subsequent studies demonstrated that cyclic variants of these linear peptides, termed cyclic citrullinated peptides (CCP) were as specific for RA but with a higher sensitivity than the linear peptides.12 In an effort to further improve the sensitivity of the CCP test, a dedicated library of citrulline-containing peptides was screened with RA sera and a new set of peptides (CCP2) was discovered which gave superior performance compared to the CCP1 test.13 Over the last few years many published reports have confirmed the diagnostic performance of the CCP2 test.14 Anti-CCP antibodies, which are also often termed as anti-citrullinated protein/peptide antibodies (ACPA’s), have been found to be present very early in the disease, often with the absence of clinical symptoms and many reports indicate that elevated levels of anti-CCP antibodies can predict the development of erosive disease.15,16,17,18,19,20 These findings suggest an important role for cyclic citrullinated peptides in the diagnosis of RA at an early stage of the disease course.