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Rheumatoid factor and anticitrullinated protein antibodies in rheumatoid arthritis: diagnostic value, associations with radiological progression rate, and extra-articular manifestations

L De Rycke¹, I Peene¹, I E A Hoffman¹, E Kruithof¹, A Union², L Meheus², K Lebeer², B Wyns⁴, C Vincent³, H Mielants¹, L Boullart⁴, G Serre³, E M Veys¹, F De Keyser¹

¹ Department of Rheumatology, Ghent University Hospital, Ghent, Belgium
² Innogenetics NV, Ghent, Belgium
³ Institut National de la Santé et de la Recherche Medicale (INSERM CJF 96-02, IFR30), Purpan School of Medicine, University of Toulouse III, Toulouse, France
⁴ Department of Electrical Energy, Systems, and Automation, Ghent University, Ghent, Belgium

Correspondence to:
Correspondence to:
Dr L De Rycke
Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium; leen.derycke{at}ugent.be

Background: Autoantibodies such as rheumatoid factor (RF) and anticitrullinated protein antibodies can be detected in rheumatoid arthritis (RA) sera.

Objective: To determine the diagnostic values of RF, anticitrullinated protein antibodies, and the shared epitope (SE), and their associations with radiological progression rates and extra-articular manifestations.

Methods: Population 1 consisted of sera from 315 patients, consecutively sent for detection of anticitrullinated protein antibodies, of which 264 were used to determine the sensitivity and specificity of RF and of antibodies against three synthetic citrullinated peptides: peptide A (pepA), peptide B (pepB), and CCP2. Population 2 consisted of sera from 180 longstanding RA patients and was used to determine associations of RA associated antibodies and the SE with radiological progression rates and extra-articular manifestations. Antibodies to pepA and pepB were detected by line immunoassay, and antibodies to CCP2 by ELISA. HLA Class II typing was performed by LiPA.

Results: In population 1, we defined adapted cut offs corresponding to a specificity of 98.5%. This yielded the following sensitivities: RF 12.8%; anti-pepA antibodies 63.6%; anti-pepB antibodies 54.2%; and anti-CCP2 antibodies 73.7%. In population 2, significant differences in radiological progression rates were found between positive and negative patients for different RA antibodies and the SE. RF, but not anticitrullinated protein antibodies or the SE, were more frequent in patients with extra-articular manifestations.

Conclusion: A valid comparison of RA associated antibodies shows superior sensitivity of the anticitrullinated protein antibodies compared with RF. The presence of RA associated antibodies and the SE are indicative for poorer radiological outcome, and presence of extra-articular manifestations is associated with RF but not with anticitrullinated protein antibodies.

Abbreviations: ACR, American College of Rheumatology; CCP, cyclic citrullinated peptide; RA, rheumatoid arthritis; RF, rheumatoid factor; ROC, receiver operating characteristic; SE, shared epitope

Keywords: anti-citrullinated protein antibodies; diagnostic value; extra-articular manifestations; radiological progression rate; rheumatoid factor

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