Camille P Figueiredo1,2, Holger Bang3, Jayme Fogagnolo Cobra4, Matthias Englbrecht1, Axel J Hueber1, Judith Haschka5, Bernhard Manger1, Arnd Kleyer1, Michaela Reiser1, Stephanie Finzel1, Hans-Peter Tony6, Stefan Kleinert7, Joerg Wendler7, Florian Schuch7, Monika Ronneberger7, Martin Feuchtenberger8, Martin Fleck9, Karin Manger10, Wolfgang Ochs11, Matthias Schmitt-Haendle11, Hanns-Martin Lorenz12,13, Hubert Nuesslein14, Rieke Alten15, Joerg Henes16, Klaus Krueger17, Jürgen Rech1, Georg Schett1. 1. Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany. 2. Division of Rheumatology, Universidade des Sao Paulo, Sao Paulo, Brazil. 3. Orgentec Diagnostika GmbH, Mainz, Germany. 4. Instituto de Reumatologia de Sao Paulo, Sao Paulo, Brazil. 5. Department of Internal Medicine 2, The Vinforce Study Group, Saint Vincent Hospital, Vienna, Austria. 6. Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany. 7. Rheumatology Practice, Erlangen, Germany. 8. Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen, Germany. 9. Department of Rheumatology and Clinical Immunology, Asklepios Medical Center Bad Abbach, Germany. 10. Rheumatology Practice, Bamberg, Germany. 11. Rheumatology Practice, Bayreuth, Germany. 12. Division of Rheumatology, Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany. 13. ACURA Center for Rheumatic Diseases Baden-Baden, Baden-Baden, Germany. 14. Rheumatology Practice, Nuremberg, Germany. 15. Schlosspark Clinic, Berlin, Germany. 16. Department of Internal Medicine 2, University of Tubingen, Tubingen, Germany. 17. Rheumatology Practice, Munich, Germany.
Abstract
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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