Abstract
Anti-citrullinated peptide/protein antibodies (ACPAs) are the most specific serological biomarkers for rheumatoid arthritis (RA). They have both diagnostic and prognostic value, and are related to more aggressive joint disease in RA. However, a single biomarker cannot differentiate RA subtypes. So, simultaneous analysis of target citrullinated peptides, using a multiplex array based on chimeric peptides composed of several domains of human proteins, could be useful. In this work, eight chimeric peptides and the corresponding native arginine-containing control peptides were obtained by solid-phase peptide synthesis. The study included RA and psoriatic arthritis (PsA) patients attending the Rheumatology Unit of the Hospital Clinic in Barcelona, as well as healthy blood donors (BD) at the same hospital. Our main aim was to explore the diagnostic value of the novel multiplex array compared to a commercial ELISA-based ACPA assay in a serum-saving way. Using the combination of the eight chimeric peptide antigens in the multiplex array, 61.4% of the RA cohort were positive for 3 or more peptides; while, the healthy BD and PsA cohorts did not show any reactivity with the tested peptides. These results indicate that we have developed a highly specific multiplex assay based of chimeric citrullinated peptides derived from filaggrin, fibrin, vimentin and human enolase proteins for the detection of ACPAs in a serum-saving way.
Highlights
Rheumatoid arthritis (RA) is a chronic and incapacitating inflammatory disease of the joints which is estimated to affect 0.5%-1% of the population worldwide
They were composed of citrullinated peptides derived from filaggrin, fibrin (617–631), vimentin (47–72) and enolase (CEP-1), and we refer to them as chimeric fibrin/enolase citrullinated peptide (CFECP), chimeric vimentin/enolase citrullinated peptide (CVECP) and chimeric enolase/filaggrin citrullinated peptide (CEFCP)
We have develop a novel multiplex platform composed of eight chimeric citrullinated peptides derived from human proteins that abound in rheumatoid synovial, and we have evaluated its suitability to detect anti-citrullinated peptide/protein antibodies (ACPAs) in serum samples of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients, as well as in healthy blood donors
Summary
Rheumatoid arthritis (RA) is a chronic and incapacitating inflammatory disease of the joints which is estimated to affect 0.5%-1% of the population worldwide. As symptoms do not always appear in the early stages of the disease, there is a clear need to improve both the precision of specific tests for its diagnosis, and its early differentiation from other rheumatic diseases that affect the articulations and connective tissue. This is especially so in the case of patients with a poor prognosis or those in the early developmental stages of the disease.
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