Clinical significance: Rheumatoid arthritis (RA) is one of the most common autoimmune diseases and also the most frequent chronic inflammatory arthropathy. The disease affects around 1% of the world population, 75% of which are female. It is characterised by inflammation of the synovial membrane, which spreads symmetrically from the small to large joints leading to the destruction of the joints in the late phase accompanied by a systemic involvement of the soft tissue. Initial symptoms include painful swelling of the metacarpophalangeal joints with morning stiffness in the joints.
The most commonly performed serological test in suspected RA cases is the determination of rheumatoid factors (RF) in addition to general inflammatory parameters. RF are antibodies (predominantly of class IgM) which react with gamma globulins and occur in 60-80% of RA patients. RF are a sensitive, but not very specific marker for RA since they also occur in healthy individuals, e.g. in various infections or other autoimmune diseases such as systemic lupus erythematosus, Sjögren’s syndrome and scleroderma. In 40-60% of RA patients autoantibodies against epidermal filaggrin (RA keratin, anti-perinuclear factor) are also exhibit in their serum. Filaggrin is a protein of the epidermis, which links keratin filaments to one another. Autoantibodies against filaggrin are detected by indirect immunofluorescence: the antigen substrate rat oesophagus shows staining of the stratum corneum (RA keratin) on the luminal side; anti-perinuclear factors (APF) are apparent in the cytoplasmic inclusion bodies of human epithelial cells of the oral mucosa.
In recent years it has been shown that the rare amino acid citrulline, which is present in filaggrin, is a substantial component of the antigenic epitope. A direct comparison study demonstrated that the sensitivity can be increased from 49% to 68% by using cyclic citrullinated peptides instead of linear citrullinated peptides as a substrate.
Antibodies against CCP occur independently of rheumatoid factors. Antibodies against CCP are predominantly of IgG class and have a specificity of 95% for RA. They can be found in the serum of 70-80% of patients very early during the development of the disease, often even many years before the onset of the first symptoms. The earlier the diagnosis is established, the earlier a suitable therapy can be started.
Anti-CCP (IgG) assay is the screening method of choice for RA disease. This test is used as an aid in the diagnosis of RA disease, in conjunction with other laboratory and clinical findings.