Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Apr;66(4):511-6.
doi: 10.1136/ard.2006.058933. Epub 2006 Sep 19.

Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: citrulline-dependent or not?

A Vannini  1 , K Cheung, M Fusconi, J Stammen-Vogelzangs, J P H Drenth, A C Dall'Aglio, F B Bianchi, L E Bakker-Jonges, W J van Venrooij, G J M Pruijn, A J W Zendman
Affiliations

Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: citrulline-dependent or not?

A Vannini et al. Ann Rheum Dis. 2007 Apr.

Abstract

Background: Antibodies directed against citrullinated proteins (eg anti-cyclic citrullinated peptide (CCP)) have excellent diagnostic and good prognostic potential for rheumatoid arthritis. Type 1 autoimmune hepatitis (AIH-1) is a chronic liver disease characterised by a variety of serum autoantibodies. Recently, in a large group of patients with AIH-1 without clear rheumatoid arthritis overlap, a relatively high percentage (9%) of anti-CCP2 positivity was scored.

Objectives: To characterise the citrulline-dependence of the observed anti-CCP2 positivity in AIH-1 sera as well as in other groups of patients without rheumatoid arthritis (mainly rheumatic diseases).

Methods: Serum samples of 57 patients with AIH-1 and 66 patients without rheumatoid arthritis, most of them reported as anti-CCP positive, were tested for citrulline-specific reactivity with a second generation anti-CCP kit, with the citrullinated and the corresponding non-citrullinated (arginine-containing) antigen. A subset of AIH-1 sera was also tested with a CCP1 ELISA (and arginine control).

Results: The anti-CCP2 reactivity of most non-rheumatoid arthritis rheumatic diseases samples (87-93%) was citrulline-specific, whereas a relatively high percentage of AIH-1 samples (42-50%) turned out to be reactive in a citrulline-independent manner. The use of citrullinated and non-citrullinated CCP1 peptides confirmed a high occurrence of citrulline-independent reactivity in AIH-1 samples.

Conclusions: In rheumatoid arthritis and most non-rheumatoid arthritis rheumatologic disease sera, anti-CCP positivity is citrulline-dependent. However in some patients, particularly patients with AIH-1, citrulline-independent reactivity in the anti-CCP2 test can occur. A positive CCP test in a non-rheumatic disease (eg liver disease) should therefore be interpreted with care, and preferably followed by a control ELISA with a non-citrullinated antigen.

PubMed Disclaimer

Conflict of interest statement

Competing interests: None declared.

References

    1. Pruijn G J M, Vossenaar E R, Drijfhout J W, van Venrooij W J, Zendman A J W. Anti‐CCP antibody detection facilitates early diagnosis and prognosis of rheumatoid arthritis. Curr Rheum Rev 200511–7.
    1. Zendman A J W, Vossenaar E R, van Venrooij W J. Autoantibodies to citrullinated (poly) peptides: a key diagnostic and prognostic marker for rheumatoid arthritis. Autoimmunity 200437295–299. - PubMed
    1. Vossenaar E R, Zendman A J W, van Venrooij W J, Pruijn G J M. PAD, a growing family of citrullinating enzymes: genes, features and involvement in disease. Bioessays 2003251106–1118. - PubMed
    1. van Venrooij W J, Zendman A J W, Pruijn G J M. Autoantibodies to citrullinated antigens in (early) rheumatoid arthritis. Autoimmun Rev 2006637–41. - PubMed
    1. Rantapää‐Dahlqvist S, de Jong B A, Berglin E, Hallmans G, Wadell G, Stenlund H.et al Antibodies against cyclic citrullinated peptide and IgA rheumatoid factor predict the development of rheumatoid arthritis. Arthritis Rheum 2003482741–2749. - PubMed

Publication types

MeSH terms