Diagnostic Utility of Anti MCV Antibodies,Anti CCPantibodies and RF in RA

Overview

Rheumatoid arthritis (RA) is a chronic systemic disease affecting primarily the synovium, leading to joint damage and bone destruction(Gravallese E,2002). It is probably the most common autoimmune disease, It is three times more common in women compared to men and usually appears in middle age(poulsom and charles, 2016) .Early diagnosis of RA and its early treatment with disease-modifying anti rheumatic drugs lead to better control and less joint damage .therefore,It is very important to find an acceptable serological marker in order to make an early diagnosis and initiate early treatment to avoid complication and disability ( Orozco C,and Olsen,2006) Various serum biomarkers are used to diagnose RA, including many autoantibodies. However, only rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) antibodies have wide acceptance (taylor et 2011).

Antibodies targeting citrullinated proteins are found to be highly specific for the diagnosis of RA (Riedmannet al,2005). Citrullinated antigens are thought to play a pivotal role in the pathogenesis of RA as they are expressed in inflamed joints and, anti-citrullinated protein antibodies are present before clinical disease and are highly specific for RA(van Gaalen et al,2005). These autoantibodies predict clinical and radiological severity and may be implicated in the pathogenesis of RA ;however, they have a high value in the early diagnosis and early treatment of RA ( Agrawal et al ,2007). Indeed, it has been demonstrated that anti-citrullinated protein antibodies are produced by plasma cells in the synovial tissue, as concentrations are more than seven fold higher in synovial tissue than in serum (Masson et al,2000). Rheumatoid factor is not specific to RA, as it is present in patients suffering from other autoimmune and infectious diseases, also found in apparently healthy elderly patients(urusm et al, 2008). Anti- CCP has been shown to be a specific prognostic marker for RA and predict the erosive or non-erosive progression of the disease. Overall, anti-CCP antibodies are a useful marker for aiding the diagnosis of early RA, especially in seronegative(RF negative)( poulsom and charles,2007) Thus, it is a useful tool for the optimal therapeutic management of RA patients. The diagnosis of RA has been improved by the introduction of other standardized immunoassays for the detection of auto-antibodies against different citrullinated antigens as anti-mutated citrullinated vimentin antibodies .Anti-MCV antibodies have been recommended to be better diagnostic marker for early arthritis (Luime et al,2010). Vimentin is an intermediate filament that is widely expressed by mesenchymal cells \&Macrophages and easy to detect in the synovium. Modification of the protein occurs in macrophages undergoing apoptosis, and antibodies to citrullinated vimentin may emerge if the apoptotic material inadequately cleared(Khalifa et ai 2013). A significant correlation has been established between anti-MCV antibodies titers and both the severity of RA and the disease-activity score (DAS28) ,anti-MCV-positive patients exhibited significantly lower reduction in disease activity and a greater number of swollen joints. Thus, it appears that, anti-MCV antibodies may have the advantage of correlating better with disease activity and patient outcome(Al-Shukaili et al,2012) The anti-mutated citrullinated vimentin antibody ELISA isa recently developed assay for the detection of IgG antibodies to a vimentin-based peptide .Anti-MCV antibody has been reported with a sensitivity of 65-82%, specificity of 80-95%.Anti-MCV antibody concentrations have also been reported as correlating with disease activity score , prognostic for disease severity, and being treatment sensitive, enabling their use in monitoring response to therapy (Bang et al,2006)