Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: Citrulline-dependent or not?
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 wilh 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.
|Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Vannini, A, Cheung, K, Fusconi, M, Stammen-Vogelzangs, J, Drenth, J.P.H, Dall'Aglio, A.C, … Zendman, A.J.W. (2007). Anti-cyclic citrullinated peptide positivity in non-rheumatoid arthritis disease samples: Citrulline-dependent or not?. Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases, 66(4), 511–516. doi:10.1136/ard.2006.058933