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Antimodified protein antibody response pattern influences the risk for disease relapse in patients with rheumatoid arthritis tapering disease modifying antirheumatic drugs
  1. Camille P Figueiredo1,2,
  2. Holger Bang3,
  3. Jayme Fogagnolo Cobra4,
  4. Matthias Englbrecht1,
  5. Axel J Hueber1,
  6. Judith Haschka5,
  7. Bernhard Manger1,
  8. Arnd Kleyer1,
  9. Michaela Reiser1,
  10. Stephanie Finzel1,
  11. Hans-Peter Tony6,
  12. Stefan Kleinert7,
  13. Joerg Wendler7,
  14. Florian Schuch7,
  15. Monika Ronneberger7,
  16. Martin Feuchtenberger8,
  17. Martin Fleck9,
  18. Karin Manger10,
  19. Wolfgang Ochs11,
  20. Matthias Schmitt-Haendle11,
  21. Hanns-Martin Lorenz12,13,
  22. Hubert Nuesslein14,
  23. Rieke Alten15,
  24. Joerg Henes16,
  25. Klaus Krueger17,
  26. Jürgen Rech1,
  27. Georg Schett1
  1. 1Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany
  2. 2Division of Rheumatology, Universidade des Sao Paulo, Sao Paulo, Brazil
  3. 3Orgentec Diagnostika GmbH, Mainz, Germany
  4. 4Instituto de Reumatologia de Sao Paulo, Sao Paulo, Brazil
  5. 5Department of Internal Medicine 2, The Vinforce Study Group, Saint Vincent Hospital, Vienna, Austria
  6. 6Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany
  7. 7Rheumatology Practice, Erlangen, Germany
  8. 8Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen, Germany
  9. 9Department of Rheumatology and Clinical Immunology, Asklepios Medical Center Bad Abbach, Germany
  10. 10Rheumatology Practice, Bamberg, Germany
  11. 11Rheumatology Practice, Bayreuth, Germany
  12. 12Division of Rheumatology, Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
  13. 13ACURA Center for Rheumatic Diseases Baden-Baden, Baden-Baden, Germany
  14. 14Rheumatology Practice, Nuremberg, Germany
  15. 15Schlosspark Clinic, Berlin, Germany
  16. 16Department of Internal Medicine 2, University of Tubingen, Tubingen, Germany
  17. 17Rheumatology Practice, Munich, Germany
  1. Correspondence to Professor Georg Schett, Department of Internal Medicine 3, Rheumatology and Immunology, University Clinic of Erlangen-Nuremberg, Erlangen; Ulmenweg 18, Erlangen 91054, Germany; georg.schett{at}


Objective To perform a detailed analysis of the autoantibody response against post-translationally modified proteins in patients with rheumatoid arthritis (RA) in sustained remission and to explore whether its composition influences the risk for disease relapse when tapering disease modifying antirheumatic drug (DMARD) therapy.

Methods Immune responses against 10 citrullinated, homocitrullinated/carbamylated and acetylated peptides, as well as unmodified vimentin (control) and cyclic citrullinated peptide 2 (CCP2) were tested in baseline serum samples from 94 patients of the RETRO study. Patients were classified according to the number of autoantibody reactivities (0–1/10, 2–5/10 and >5/10) or specificity groups (citrullination, carbamylation and acetylation; 0–3) and tested for their risk to develop relapses after DMARD tapering. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining the role of autoantibodies in predicting relapse.

Results Patients varied in their antimodified protein antibody response with the extremes from recognition of no (0/10) to all antigens (10/10). Antibodies against citrullinated vimentin (51%), acetylated ornithine (46%) and acetylated lysine (37%) were the most frequently observed subspecificities. Relapse risk significantly (p=0.011) increased from 18% (0–1/10 reactivities) to 34% (2–5/10) and 55% (>5/10). With respect to specificity groups (0–3), relapse risk significantly (p=0.021) increased from 18% (no reactivity) to 28%, 36% and finally to 52% with one, two or three antibody specificity groups, respectively.

Conclusions The data suggest that the pattern of antimodified protein antibody response determines the risk of disease relapse in patients with RA tapering DMARD therapy.

Trial registration number 2009-015740-42; Results.

  • Ant-CCP
  • Rheumatoid Arthritis
  • Treatment

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  • Handling editor Tore K Kvien

  • Contributors JFC, AJH, BM, AK, MR, H-PT, SK, JW, FS, MR, MFe, MFl, KM, WO, MS-H, H-ML, HN, RA, JH and KK collected the data. CPF, HB and JH analysed the data. ME performed statistical analyses. SF, AJH, JR and GS designed the study. CPF, HB and GS wrote the manuscript.

  • Funding This study was supported by the Deutsche Forschungsgemeinschaft (SPP1468-IMMUNOBONE; CRC1181), the Bundesministerium für Bildung und Forschung (BMBF; project METARTHROS), the Marie Curie project OSTEOIMMUNE, the TEAM project of the European Union and the IMI funded project BTCure. CPF was supported by Ciencias sem Frontieras from the Conselho Nacional de Desenvolvimento Cientifico e Teconologico do Brasil (CNPq 200175/2014-9).

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the ethical committee of the University Clinic of Erlangen.

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