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Extended report
The ACPA isotype profile reflects long-term radiographic progression in rheumatoid arthritis
  1. Diane van der Woude1,
  2. Silje W Syversen2,
  3. Ellen I H van der Voort1,
  4. Kirsten N Verpoort1,
  5. Guro L Goll2,
  6. Michael P M van der Linden1,
  7. Annette H M van der Helm-van Mil1,
  8. Désirée M F M van der Heijde1,2,
  9. Tom W J Huizinga1,
  10. Tore K Kvien2,
  11. René E M Toes1
  1. 1Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  2. 2Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  1. Correspondence to Dr Diane van der Woude, Department of Rheumatology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands; dvanderwoude{at}


Background The presence of anti-citrullinated protein antibodies (ACPA) is a powerful predictive factor for the development and progression of rheumatoid arthritis (RA). The ACPA response has been shown to consist of various isotypes, but the consequences of differences in isotype distribution have not been extensively investigated.

Objective To investigate the relationship between ACPA isotypes, disease progression and radiological outcome.

Methods ACPA isotypes were determined in sera of anti-cyclic citrullinated peptide 2-positive patients by enzyme-linked immunosorbent assay (ELISA). To investigate whether the ACPA response continues to evolve during disease development, the ACPA isotype profile during progression of undifferentiated arthritis (UA) to RA was studied. The association of disease progression with ACPA isotype use was assessed using long-term radiographic follow-up data from patients with RA in two independent cohorts.

Results The ACPA isotype distribution did not expand during disease progression from UA to RA, but was relatively stable over time. In both RA cohorts, the baseline ACPA isotype profile was a significant predictor of disease severity, with more isotypes indicating a higher risk of radiographic damage (odds ratio for every additional isotype: 1.4 (95% CI 1.1 to 1.9) p<0.001). ACPA isotypes supplied additional prognostic information to ACPA status alone, even after correction for other predictive factors.

Conclusions The magnitude of the ACPA isotype profile at baseline reflects the risk of future radiographic damage. These results indicate that the presence and the constitution of the ACPA response are relevant to the disease course of RA.

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  • DW and SWS contributed equally.

  • Funding DW is supported by the Dutch Organisation for Scientific Research (AGIKO grant). SWS is supported by grants from the Eastern Norway Regional Health Authority. AHMHM is supported by the Netherlands Organisation of Health Research and Development. REMT is supported by the Dutch Organisation for Scientific Research (VIDI and VICI grant). The project was partly funded through Coordination Theme 1 (Health) of the European Community FP7: Masterswitch (project number 223404), and FP6: Autocure, as well as through funding by the Dutch Arthritis Foundation. The funding sources had no involvement in the collection, analysis and interpretation of the data, or in the writing of the report.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the ethics committee of the LUMC and regional Norwegian ethics committee for the EURIDISS.

  • Provenance and peer review Not commissioned; externally peer reviewed.