Antimodified protein antibody response pattern influences the risk for disease relapse in patients with rheumatoid arthritis tapering disease modifying antirheumatic drugs.
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.


BACKGROUND
2009-015740-42; Results.
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.|Division of Rheumatology, Universidade des Sao Paulo, Sao Paulo, Brazil.
Camille P
CP
Figueiredo
Orgentec Diagnostika GmbH, Mainz, Germany.
Holger
H
Bang
Instituto de Reumatologia de Sao Paulo, Sao Paulo, Brazil.
Jayme Fogagnolo
JF
Cobra
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Matthias
M
Englbrecht
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Axel J
AJ
Hueber
Department of Internal Medicine 2, The Vinforce Study Group, Saint Vincent Hospital, Vienna, Austria.
Judith
J
Haschka
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Bernhard
B
Manger
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Arnd
A
Kleyer
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Michaela
M
Reiser
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Stephanie
S
Finzel
Department of Internal Medicine 2, University of Wurzburg, Wurzburg, Germany.
Hans-Peter
HP
Tony
Rheumatology Practice, Erlangen, Germany.
Stefan
S
Kleinert
Rheumatology Practice, Erlangen, Germany.
Joerg
J
Wendler
Rheumatology Practice, Erlangen, Germany.
Florian
F
Schuch
Rheumatology Practice, Erlangen, Germany.
Monika
M
Ronneberger
Rheumatology Practice and Department of Internal Medicine 2, Clinic Burghausen, Burghausen, Germany.
Martin
M
Feuchtenberger
Department of Rheumatology and Clinical Immunology, Asklepios Medical Center Bad Abbach, Germany.
Martin
M
Fleck
Rheumatology Practice, Bamberg, Germany.
Karin
K
Manger
Rheumatology Practice, Bayreuth, Germany.
Wolfgang
W
Ochs
Rheumatology Practice, Bayreuth, Germany.
Matthias
M
Schmitt-Haendle
Division of Rheumatology, Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany.|ACURA Center for Rheumatic Diseases Baden-Baden, Baden-Baden, Germany.
Hanns-Martin
HM
Lorenz
Rheumatology Practice, Nuremberg, Germany.
Hubert
H
Nuesslein
Schlosspark Clinic, Berlin, Germany.
Rieke
R
Alten
Department of Internal Medicine 2, University of Tubingen, Tubingen, Germany.
Joerg
J
Henes
Rheumatology Practice, Munich, Germany.
Klaus
K
Krueger
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Jürgen
J
Rech
Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany.
Georg
G
Schett
D000085:Acetates / Q000276:immunology; D000107:Acetylation; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002219:Carbamates / Q000276:immunology; D002956:Citrulline / Q000031:analogs & derivatives / Q000276:immunology; D006801:Humans; D016015:Logistic Models; D008239:Lysine / Q000276:immunology; D015999:Multivariate Analysis; D009952:Ornithine / Q000276:immunology; D010455:Peptides / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D012008:Recurrence; D014746:Vimentin / Q000276:immunology
D000085:Acetates; D018501:Antirheumatic Agents; D001323:Autoantibodies; D002219:Carbamates; D010455:Peptides; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide; C001352:homocitrulline; D002956:Citrulline; D009952:Ornithine; D008239:Lysine
Ant-CCP; Rheumatoid Arthritis; Treatment