Open Access Highly Accessed Research article

Diagnostic and prognostic value of antibodies against chimeric fibrin/filaggrin citrullinated synthetic peptides in rheumatoid arthritis

Raimon Sanmartí1*, Eduard Graell2, Maria L Perez3, Guadalupe Ercilla4, Odette Viñas4, Jose A Gómez-Puerta1, Jordi Gratacós2, Alejandro Balsa5, Maria J Gómara3, Marta Larrosa2, Juan D Cañete1 and Isabel Haro3

Author Affiliations

1 Rheumatology Service, Hospital Clínic of Barcelona, IDIBAPS, Villarroel 170, 08036 Barcelona, Spain

2 Rheumatology Unit, Hospital Universitari Parc Taulí of Sabadell, Parc Taulí s/n 08208 Sabadell, Barcelona, Spain

3 Unit of Synthesis and Biomedical Applications of Peptides IQAC-CSIC, Jordi Girona 18-26, 08034, Barcelona, Spain

4 Immunology Service, Hospital Clínic of Barcelona, Villarroel 170, 08036 Barcelona, Spain

5 Rheumatology Service, Hospital Universitario La Paz, Paseo de la Castellana 261, 28046 Madrid, Spain

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Arthritis Research & Therapy 2009, 11:R135  doi:10.1186/ar2802

Published: 2 September 2009

Abstract

Introduction

Evidence suggests that citrullinated fibrin(ogen) may be a potential in vivo target of anticitrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis (RA). We compared the diagnostic yield of three enzyme-linked immunosorbent assay (ELISA) tests by using chimeric fibrin/filaggrin citrullinated synthetic peptides (CFFCP1, CFFCP2, CFFCP3) with a commercial CCP2-based test in RA and analyzed their prognostic values in early RA.

Methods

Samples from 307 blood donors and patients with RA (322), psoriatic arthritis (133), systemic lupus erythematosus (119), and hepatitis C infection (84) were assayed by using CFFCP- and CCP2-based tests. Autoantibodies also were analyzed at baseline and during a 2-year follow-up in 98 early RA patients to determine their prognostic value.

Results

With cutoffs giving 98% specificity for RA versus blood donors, the sensitivity was 72.1% for CFFCP1, 78.0% for CFFCP2, 71.4% for CFFCP3, and 73.9% for CCP2, with positive predictive values greater than 97% in all cases. CFFCP sensitivity in RA increased to 80.4% without losing specificity when positivity was considered as any positive anti-CFFCP status. Specificity of the three CFFCP tests versus other rheumatic populations was high (> 90%) and similar to those for the CCP2. In early RA, CFFCP1 best identified patients with a poor radiographic outcome. Radiographic progression was faster in the small subgroup of CCP2-negative and CFFCP1-positive patients than in those negative for both autoantibodies. CFFCP antibodies decreased after 1 year, but without any correlation with changes in disease activity.

Conclusions

CFFCP-based assays are highly sensitive and specific for RA. Early RA patients with anti-CFFCP1 antibodies, including CCP2-negative patients, show greater radiographic progression.