Anti–citrullinated protein antibody
Anti-citrullinated protein antibodies (ACPAs) are
During inflammation,
ACPAs have proved to be powerful biomarkers that allow the diagnosis of rheumatoid arthritis (RA) to be made at a very early stage.[1]
In July 2010, the 2010 ACR/EULAR Rheumatoid Arthritis Classification Criteria were introduced.
History
The presence of autoantibodies against citrullinated proteins in rheumatoid arthritis patients was first described in the mid-1970s when the biochemical basis of antibody reactivity against keratin and filaggrin was investigated.[4][5] Subsequent studies demonstrated that autoantibodies from RA patients react with a series of different citrullinated antigens, including fibrinogen, deiminated Epstein-Barr Virus Nuclear Antigen 1 and vimentin,[6][7][8] which is a member of the intermediate filament family of proteins. Several assays for detecting ACPAs were developed in the following years, employing mutated citrullinated Vimentin (MCV-assay), filaggrin-derived peptides (CCP-assay)[9][10] and viral citrullinated peptides (VCP-assay).
A 2006 clinical study showed that anti viral citrullinated peptide (VCP) antibodies of the
Clinical significance
In a comparative study (in 2007), various detection kits had a
However, novel test systems utilizing ACPA have been developed. Citrullinated vimentin is a very promising autoantigen in RA, and a suitable tool for studying this systemic autoimmune disease. Vimentin is secreted and citrullinated by macrophages in response to apoptosis, or by pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha).[15] [16] A newly developed
Given that ACPA are more specific than rheumatoid factor, they are used to distinguish various causes of arthritis.[21] Novel assays may be useful for monitoring disease activity and effects of RA therapy.[22]
The reference ranges for blood tests of anti–citrullinated protein antibodies are:
Negative | Low/weak positive | Moderate positive | High/strong positive | Unit |
< 20[23] | 20–39[23] | 40–59[23] | > 60[23] | EU[23] |
Anti-CCP is part of the 2010 ACR/EULAR classification criteria for
Combination of anti-CCP with other serological markers like rheumatoid factor, 14-3-3η (YWHAH) not only enhances the diagnostic capture rate but together with acute phase reactants either in early disease or at the time of diagnosis may be useful in predicting future outcomes.
Other ACPAs and citrullinated targets in RA
Vimentin, fibrin, filaggrin, enolase and keratin are common citrullination targets. The list of proteins that undergo citrullination and make up the citrullinome continues to increase. The RA associated citrullinome has been reported to include targets from synovial fluid and tissue that range from proteases, receptors, and carrier proteins. These proteins are components of complement, proteolytic activity, cell recognition, endocytosis, and response to biotic stimuli amongst others.[25] 14-3-3η (YWHAH) is also another synovial derived protein that has been reported as a citrullination target.[26]
References
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- ^ a b c d e chronolab.com > Autoantibodies associated with rheumatic diseases > Reference ranges Archived 30 July 2013 at the Wayback Machine Retrieved on 29 April 2010
- ^ Gardette A, Ottaviani S, Tubach F, Roy C, Nicaise-Roland P, Palazzo E, Gill G, Meyer O, Dieudé P. High anti-CCP antibody titres predict good response to rituximab in patients with active rheumatoid arthritis. Joint Bone Spine. 2014 Oct;81(5):416–20. doi: 10.1016/j.jbspin.2014.06.001. Epub 2014 Jul 3. PMID 24998790.
- ^ Tilvawala R, Nguyen SH, Maurais AJ, Nemmara VV, Nagar M, Salinger AJ, Nagpal S, Weerapana E, Thompson PR. The Rheumatoid Arthritis-Associated Citrullinome. Cell Chem Biol. 2018 Jun 21;25(6):691–704.e6. doi: 10.1016/j.chembiol.2018.03.002. Epub 2018 Apr 5. PMID 29628436; PMCID: PMC6014894.
- ^ Maksymowych WP, Marotta A. 14-3-3η: a novel biomarker platform for rheumatoid arthritis. Clin Exp Rheumatol. 2014 Sep-Oct;32(5 Suppl 85):S-35-9. Epub 2014 Oct 30. PMID 25365087.