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Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis: As Good as it Gets?

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Abstract

Anti-citrullinated protein antibodies (ACPAs) have recently emerged as sensitive and specific serological markers of rheumatoid arthritis (RA), providing superior alternative of the rheumatoid factor (RF) test in the laboratory diagnostics of RA. The first members of this autoantibody family were anti-perinuclear factor (APF) and anti-keratin antibodies (AKA). It became evident that both APF and AKA recognize citrullinated epitopes of filaggrin. Citrullination is a post-translational modification of arginine by deimination, physiologically occurring during apoptosis, inflammation or keratinization. The presence of several citrullinated proteins has been demonstrated in the RA synovium. The identification of citrullinated epitopes as targets for anti-filaggrin antibodies led to the development of the first and later second generation anti-cyclic citrullinated peptide (anti-CCP) antibody assays. The widely used anti-CCP2 assays have high diagnostic sensitivity and specificity, and they also show important predictive and prognostic value in RA. The anti-Sa antibody has been identified a decade ago; however, recent studies confirmed that anti-Sa is directed against citrullinated vimentin, hence it is a new member of the family of ACPAs. The newly developed anti-mutated citrullinated vimentin (anti-MCV) assay has similar diagnostic performance than the anti-CCP2 ELISA; however, the diagnostic spectrum of the anti-MCV test is somewhat different from that of anti-CCP2. It’s especially useful in the diagnosis of RA in RF and anti-CCP2 seronegative patients. The combined application of anti-CCP2 and anti-MCV assays can improve the laboratory diagnostics of RA. The family of ACPAs is expected to expand; there is an increasing need for developing new diagnostic strategies after careful evaluation of the characteristics of the available assays.

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Acknowledgement

This work was supported by grant no. T 048541 from the Hungarian National Scientific Research Fund (OTKA; Z.S.).

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Authors and Affiliations

  1. Division of Rheumatology, 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, 22 Moricz Street, Debrecen, H-4004, Hungary

    Zoltán Szekanecz, Lilla Soós, Zoltán Szabó, Anikó Végvári, Gabriella Szücs & Sándor Szántó

  2. Laboratory of Immunology, 3rd Department of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary

    Andrea Fekete, Anikó Kapitány, Sándor Sipka & Gabriella Lakos

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  1. Zoltán Szekanecz
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  2. Lilla Soós
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Correspondence to Zoltán Szekanecz.

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Zoltán Szekanecz and Lilla Soós with equal contribution.

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Szekanecz, Z., Soós, L., Szabó, Z. et al. Anti-Citrullinated Protein Antibodies in Rheumatoid Arthritis: As Good as it Gets?. Clinic Rev Allerg Immunol 34, 26–31 (2008). https://doi.org/10.1007/s12016-007-8022-5

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