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.
- Rheumatoid Arthritis
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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.