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Prevalence of non-rheumatoid arthritis-associated autoantibodies in sera of anti-cyclic citrulline antibody-positive patients


Serological markers, especially autoantibodies with high disease specificity, have their emphasized role in support of the diagnosis of autoimmune diseases. Detection of anti-cyclic citrulline (anti-CCP) antibodies has gained increasing interest in clinical practice as they have shown to have strikingly high (96–89%) specificity for rheumatoid arthritis (RA).


The aim of this study is to summarize our experience in testing anti-CCP and other autoantibodies on a large number of sera from patients with suspected and definite connective tissue disease.


A total of 2061 sera derived from 1750 patients were requested for detection of anti-CCP and rheumatoid factor (RF) autoantibodies. Conventional autoantibodies were also tested according to the requests of clinicians in cases of 1560 samples. Anti-CCP antibodies were detected with the ImmunoscanRA Elisa kit, and RF by nephelometry (Behring). Antinuclear antibodies were detected by IF test on Hep-2 cells (Inova). Anti-Ena antibodies, anti-DNA, anti-chromatin, anti-cardiolipin were measured using ELISA kits (Inova). Anti-CCP antibodies exceeding the level of 25 U/ml were considered positive. Samples expressing antinuclear antibodies at dilution of 1:200 or higher were evaluated.


Anti-CCP and RF were present in sera of 331 patients, while 59 patients were positive only for anti-CCP antibodies.

Autoantibody profile detected in anti-CCP-positive and RF-positive patients (n = 331) – antinuclear antibody positive samples, n = 54 (16.3%): including polimyosi-tis, scleroderma associated antibodies, n = 7 (2%); systemic lupus erythematosus associated antibodies (anti-DNA, anti-chromatin, anti-histone, anti-Sm), n = 12 (3.6%); MCTD associated antibodies, n = 5 (1.5%); Sjögren syndrome associated autoantibodies, n = 10 (3%); anti-centromere antibodies, n = 4 (1.3%); and primary biliary cirrhosis associated antibodies, antimichondrial antibody, n = 4 (1.3%). In four cases the presence of anti-neutrophyl cytoplasmic antibodies was also seen.

In the group of patients with only anti-CCP positivity (n = 59) – two (3%) samples were positive for anti-centromer, one of them for Scl70 as well, one was positive for PM/Scl like antibodies, one for anti-DNA, one for anti-Rnp/Sm antibody, and one sample showed strong antimichondrial antibody positivity.


These results show a more complex picture of the occurrence of anti-CCP antibodies as they may associate with different stages of connective tissue diseases. We also aimed to initiate further clinical studies to define the role of this family of autoantibodies in the diagnosis of RA-associated secondary diseases, and also in overlap syndromes.


This work was supported by Hungarian grant OTKA T037876.

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Brozik, M., Böhm, U., Csiki, J. et al. Prevalence of non-rheumatoid arthritis-associated autoantibodies in sera of anti-cyclic citrulline antibody-positive patients. Arthritis Res Ther 7 (Suppl 1), P155 (2005).

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