Anti-cyclic citrullinated protein antibodies: Why is this test so critical in the diagnosis of rheumatoid arthritis?

With the advancement of medical technology, early diagnosis of rheumatoid arthritis (RA) has become increasingly important. In recent studies, anti-cyclic citrullinated protein antibodies (ACPA) have been shown to be powerful biomarkers for RA diagnosis. This autoantibody can be detected in the serum of most RA patients, providing a possible diagnostic approach in the early stages of the disease.

Anti-cyclic citrullinated protein antibodies are autoantibodies that specifically target peptides and proteins that have been citrullinated, a process that often occurs during the body's inflammatory response.

During the inflammatory process, the amino acid arginine can be converted into citrulline by enzymes, a process called "citrulination." These changes make the original protein structure significantly different, which is recognized by the immune system as an antigen and triggers an immune response. The emergence of these antibodies not only provides a basis for clinical diagnosis, but also becomes an important indicator for predicting disease progression and therapeutic response.

History of ACPA

The discovery of anti-cyclic citrullinated protein antibodies dates back to the mid-1970s, when antibody responses to keratin and filaggrin were studied. Subsequent studies have found that autoantibodies in RA patients react with a variety of different citrulline antigens, including fibrin, deaminated Epstein-Barr virus nuclear antigen, and filaggrin.

In a 2006 clinical study, antiviral citrullinated peptide (VCP) antibodies demonstrated specificity in distinguishing RA from other similar chronic arthritis, showing independent production of antibodies of each isotype.

Clinical significance

According to a 2007 comparative study, the sensitivity of various test kits ranged from 69.6% to 77.5%, and the specificity ranged from 87.8% to 96.4%. Although the performance of these immunoassays is quite excellent, their sensitivity is comparable to that of RA factor (RF) and therefore requires further evaluation in clinical applications.

With the development of novel detection systems, citrullinated filaggrin is considered a promising autoantigen for studying this systemic autoimmune disease. Recently developed enzyme-linked immunosorbent assay (ELISA) systems utilize genetically modified citrullinated filaggrin to optimize assay performance. Recent studies have pointed out that the anti-MCV test system performs well in diagnosing anti-CCP-negative RA patients, demonstrating the clinical potential of this new detection method.

Detection value of anti-CCP

Anti-CCP antibody testing not only helps in the early diagnosis of RA, but can also be used to screen people at risk for development, such as relatives of RA patients. Although some studies have found that the concordance rate of identical twins developing RA is 15.4% and that of fraternal twins is 3.6%, this shows the influence of genetic factors in RA.

Because anti-CCP is more specific than RA factors, it plays an important role in differentiating various types of arthritis.

Other RA-related ACAs and citrullination targets

Common citrullination targets include filaggrin, fibrin, serine proteins, and keratin. With the deepening of research, more citrullinated proteins related to RA can be identified, and these proteins are involved in various functions of cells, including lytic immune response and cell recognition.

Combined detection of anti-CCR and other serological markers can also improve the diagnostic capture rate of RA and predict prognosis, such as the possibility of future imaging damage and therapeutic response, showing the importance of diversity in RA diagnosis. How to further improve the application and effectiveness of these diagnostic tools will be a key direction for future research?

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