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From the 1970s to today: Why have anti-cyclic citrullinated antibodies become a core weapon in the diagnosis of rheumatoid arthritis?
Anti-cyclic citrullinated antibodies (ACPAs) are a type of autoantibodies that target self-proteins, mainly those peptides and proteins that have been citrullinated. Such antibodies can be detected in the serum or plasma of most patients with rheumatoid arthritis (RA). As rheumatoid arthritis progresses, these antibodies gradually become important indicators for clinical diagnosis and can even be detected in the early stages of the disease.
During inflammation, the arginine amino acid can be enzymatically converted to citrulline through a process called citrullination, which may change the shape of the protein so that it is viewed as an antigen by the immune system, thereby producing immune response.
Historical background
The existence of anti-citrullinated protein antibodies was first described in the mid-1970s, when researchers explored antibody responses to keratin and skin peroxidase. As the research progressed, scientists discovered that autoantibodies in RA patients reacted with a variety of different citrullinated antigens, including fibrin, deaminated Epstein-Barr virus nuclear antigen 1, and members of the intermediate fiber family. Cellular protein---Vimenin.
Since the mid-1970s, the scientific community has worked to find assays using ACPAs, including mutated citrullinated vemenin (MCV assay), keratin-derived peptides (CCP assay), and viral citrullin Aminated peptides (VCP detection).
Clinical importance
According to a comparative study conducted in 2007, the sensitivity of various testing tools ranged from 69.6% to 77.5%, while the specificity ranged from 87.8% to 96.4%. Although the performance of these immune tests is very superior, such as the CCP test, their sensitivity is comparable to that of rheumatoid factor (RF). Analyzes of the relationship between the title of anti-CCP antibodies and disease activity in RA have yielded inconsistent results.
With the development of new testing systems, detection using ACPAs presents greater possibilities. Currently, vitamin is considered very promising as an autoantigen for RA and an important tool for studying this systemic autoimmune disease.
A newly developed enzyme-linked immunosorbent assay system (ELISA) makes full use of genetically modified citrullinated vitamin (MCV) to optimize the performance of the test. Of note, a recently published study overestimated the value of an anti-MCV detection system for rheumatoid arthritis diagnosis in anti-CCP-negative patients.
Anti-CCP is not only useful for the early diagnosis of rheumatoid arthritis, but is indeed helpful especially in high-risk groups, such as relatives of RA patients. The study by Silman et al. showed that the concordance rate of identical twins was 15.4%, while that of fraternal twins was 3.6%. Because ACPAs are more specific than rheumatoid factors, they can be used to differentiate between different causes of arthritis.
Other ACPAs and citrulline targets in RA
Common citrulline targets include vitamin, cellulose, keratin, etc. As research on citrullinated proteins continues to deepen, the list of citrullinated proteins related to RA is also expanding. These proteins not only participate in multiple biological processes such as the complement system, proteolytic activity, cell recognition, endocytosis, etc., but are also closely related to the response of the immune system.
For example, 14-3-3eta (YWHAH), also a synovial-derived protein, has been reported as a target for citrullination, suggesting the potential these targets may have in the diagnosis and treatment of RA.
Over time, the discovery and application of anti-cyclic citrullinated antibodies not only improved the diagnostic capabilities of rheumatoid arthritis, but also provided a new perspective for studying the cause and treatment of the disease. In the early diagnosis and treatment of rheumatoid arthritis, the role of this type of autoantibodies is becoming increasingly important. How will future research further reveal its potential and challenges? Is it worth pondering?
