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ACPA epitopes — what are we actually looking at?

Nature Reviews Rheumatologyvolume 15pages130132 (2019) | Download Citation

The use of assays to detect anti-citrullinated protein antibodies (ACPAs) is helpful in the diagnosis of rheumatoid arthritis. But how good are these assays at detecting ACPAs and do we really know what the results are telling us about ACPA specificity?

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  1. 1.

    Lundberg, K. et al. Citrullinated proteins have increased immunogenicity and arthritogenicity and their presence in arthritic joints correlates with disease severity. Arthritis Res. Ther. 7, R458–R467 (2005).

  2. 2.

    Kuhn, K. A. et al. Antibodies against citrullinated proteins enhance tissue injury in experimental autoimmune arthritis. J. Clin. Invest. 116, 961–973 (2006).

  3. 3.

    Cornilett, M. et al. Seropositivity and antibody profiling of patients are dramatically impacted by the features of peptides used as immunosorbents: a lesson from anti− citrullinated protein/peptide antibody. J. Immunol. 201, 3211–3217 (2018).

  4. 4.

    Masson-Bessière, C. et al. The major synovial targets of the rheumatoid arthritis-specific antifilaggrin autoantibodies are deiminated forms of the α- and β-chains of fibrin. J. Immunol. 166, 4177–4184 (2001).

  5. 5.

    Sebbag, M. et al. Epitopes of human fibrin recognized by the rheumatoid arthritis-specific autoantibodies to citrullinated proteins. Eur. J. Immunol. 36, 2250–2263 (2006).

  6. 6.

    Schellekens, G. A. et al. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J. Clin. Invest. 101, 273–281 (1998).

  7. 7.

    Hafkenscheid, L. et al. Structural analysis of variable domain glycosylation of anti-citrullinated protein antibodies in rheumatoid arthritis reveals the presence of highly sialylated glycans. Mol. Cell. Proteomics 16, 278–287 (2017).

  8. 8.

    Schellekens, G. A. et al. The diagnostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum. 43, 155–163 (2000).

  9. 9.

    Ge, C. et al. Structural basis of cross-reactivity of anti-citrullinated protein antibodies. Arthritis Rheumatol. (2018).

  10. 10.

    Pruijn, G. J., Wiik, A. & van Venrooij, W. J. The use of citrullinated peptides and proteins for the diagnosis of rheumatoid arthritis. Arthritis Res. Ther. 12, 203–211 (2010).

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Author information


  1. Amsterdam Rheumatology and Immunology Center, Amsterdam UMC, Vrije Universiteit, Amsterdam, Netherlands

    • Lotte A. van de Stadt
  2. Department of Immunopathology, Sanquin Research, Amsterdam, Netherlands

    • Theo Rispens
  3. AMC–Sanquin Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands

    • Theo Rispens


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Competing interests

The authors declare no competing interests.

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Correspondence to Theo Rispens.

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