Anti-citrullinated protein antibody
ACPAs or antibodies against citrullinated peptides / proteins (german anti- citrullinated peptide / protein antibodies, therefore, briefly: ACPA ) are autoantibodies (antibodies against components of one's body ) that occur in patients with rheumatoid arthritis. More recently, the test systems have the serological detection of ACPAs the classic serodiagnosis of the rheumatoid factors significantly improved. The most prominent representatives of the ACPA test systems are the detection of autoantibodies against mutated citrullinated vimentin ( anti-MCV ELISA ) and the CCP assay. Both reach sensitivities of nearly 80% and specificity of nearly 98%.
Basics
The discovery and identification of citrullinated autoantigens mid-1970s was a significant improvement in the serological RA diagnosis. The starting point was the discovery of so-called anti - keratin antibodies (AKA ) and the observation that the presence of these autoantibodies is highly specific for the serological diagnosis of rheumatoid arthritis.
The target antigen fillagrin has been identified, a structural protein that is formed exclusively by keratinproduzierenden epithelial cells. Further investigations showed that the AKA bind exclusively to the citrullinated fillagrin and not to the original ( non- citrullinated ) protein.
The citrullination of proteins is a physiological (ie naturally present in the body focal ) process; it is carried out enzymatically by the deamination of the amino acid arginine to the amino acid citrulline. Citrullination by the charge of the molecule, resulting in a change in the three-dimensional structure of the antigenic properties of the protein result in modified. As a result, the citrullinated, altered endogenous protein is considered by the immune system as foreign. It comes ( " directed against themselves") antibodies that attack its own tissues and bring an inflammatory reaction in the formation of autoreactive. Result is an autoimmune disease.
Importance
For certain ACPAs a correlation between the antibody titer (the " concentration " of autoantibodies in the blood serum) occupied and the disease activity, making them ideal for the treating rheumatologist at a good tool for the prognosis of the disease and a good base for the individual therapy decision makes.
ACPA are in addition to their importance for the early diagnosis also important for the prognosis of joint damage in rheumatoid arthritis. In patients with this disease and finding ACPA positive in general below the destruction of the joints making faster progress than in patients with rheumatoid arthritis without ACPA.
Historical
Once it was known that the citrulline residues are the actual sites of attack for the antibodies, a first commercial detection assay for RA diagnosis with artificially produced peptides was developed. To use this came synthetic citrullinated peptide fragments whose ends were joined together to form small peptide rings. This cyclic citrullinated peptides artificially produced form the basis of the so -called anti -CCP tests, which are still used in the routine for the diagnosis of rheumatoid arthritis.
The good diagnostic properties of the anti -citrulline - proof labels are increasingly used for the detection of antibodies to citrullinated proteins, which are not produced artificially but are synthesized in vivo, ie in the human body and also citrulliniert. It is believed today that the citrullination is an essential part of the pathogenesis ( disease development ) of rheumatoid arthritis.
Thus, for example, for the detection of antibodies against citrullinated fibrin high specificity and sensitivity for the diagnosis of early rheumatoid arthritis is, the diagnostic line capability (sensitivity 75%, specificity 98% ) of the tests similar to that of anti-CCP - evidence is. The same was also shown for the anti- fibrinogen detection in early RA as well as for the detection of antibodies against alpha - enolase. The detection of antibodies against mutated citrullinated vimentin is now recognized as a highly specific serological detection for prognosis and diagnosis just the early forms of rheumatoid arthritis.