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Abstract
Rheumatoid arthritis (RA), caused by the abnormal recognition of human joint cells by autoimmune antibodies, remains the world’s most prevalent autoimmune disease, with over five million people affected and as much as 4% of the population at risk of RA. To prevent rapid disease development, hormonal and anti-inflammatory therapies require fast and reliable RA diagnosis. However, difficulty in detecting early specific biomarkers for RA means that it is unclear when treatment needs to begin. Here, we combined synthesis of citrullinated peptide epitopes with molecular diagnostics to verify a new specific biomarker for early RA diagnosis and flare prediction. A fibrinogen-derived 21-amino-acid-long citrullinated peptide showed high reactivity toward autoantibodies in RA samples. Additionally, the level of antibodies to this epitope was elevated prior to flares. In contrast, other citrullinated protein variants had lower reactivity and poorer sensitivity to disease activity. In conclusion, fibrinogen-derived epitope E2 subjected to citrullination facilitated a reliable RA diagnosis with a strong correlation to disease activity. This is of a high value for the diagnosis and management of RA patients who respond poorly to treatment.
Highlights
Rheumatoid arthritis (RA) is one of the most common systemic inflammatory diseases; it is diagnosed in over 1% of the population [1]
To determine the novel reactivities of autoantibodies in RA patients, we developed 20 citrullinated peptide epitopes and applied them as antigens in ELISA
The epitopes originates from five previously described proteins with relevance to RA pathogenesis: fibrinogen (E1, E4, and E6), vimentin (E9 and E10), histone 3 (E11-E15), collagen (E16), and filaggrin (E17-E20; Table 1). These proteins are involved in connective tissue onto- and neogeneses, and are often affected in RA
Summary
Rheumatoid arthritis (RA) is one of the most common systemic inflammatory diseases; it is diagnosed in over 1% of the population [1]. RA diagnosis relies on clinical criteria and physical examination, including laboratory and radiographic results [2]. The RA diagnosis is typically established during its last stage. RA diagnosis is highly desired to reach the optimal therapeutic window. Anticitrullinated protein antibodies (ACPAs) are useful serological biomarker for RA diagnosis in over 50% subjects [3]. The presence of ACPA before the onset of RA symptoms can greatly advance understanding of disease pathogenesis. This knowledge may represent a milestone for early RA diagnosis and effective disease management [5]
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