The impact of autoantibodies against citrullinated, carbamylated, and acetylated peptides on radiographic progression in patients with new-onset rheumatoid arthritis: an observational cohort study

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Authors

  • Jagtar S Nijjar
  • Fraser R Morton
  • Holger Bang
  • Christopher Buckley
  • Désirée van der Heijde
  • Ashley Gilmour
  • Caron Paterson
  • Iain B McInnes
  • Duncan Porter
  • Karim Raza
  • Scottish Early Rheumatoid Arthritis Inception Cohort Investigators

Colleges, School and Institutes

Abstract

Background: A range of anti-modified protein antibodies (AMPAs) are associated with rheumatoid arthritis. We aimed to assess the relationship between AMPA profiles and radiographic progression in patients with new-onset rheumatoid arthritis. Methods: In this cohort study, we obtained samples and data from the Scottish Early Rheumatoid Arthritis (SERA) inception cohort and biobank, which recruited patients with new-onset rheumatoid arthritis or undifferentiated arthritis who had at least one swollen joint from 20 hospitals across Scotland. AMPAs in plasma samples were measured by ELISAs at baseline. Paired radiographs of the hands and feet were taken at baseline and at 1 year and were scored with the Sharp-van der Heijde (SvH) method. We calculated differences in radiographic progression using estimated marginal mean changes between baseline and 1 year, with the baseline values of radiographic variables, rheumatoid factor, sex, age at recruitment, symptom duration, and Disease Activity Score 28 with C-reactive protein included as covariates. Findings: Between March 1, 2011, and April, 30, 2015, 1073 patients were recruited to the SERA study. 362 patients with rheumatoid arthritis were included in our study and had their AMPA profiles determined. Patients were grouped into four main autoantibody profiles by reactivities to post-translational modifications: single positivity for anti-citrullinated peptide antibodies (ACPAs; 73 [20%]); double positivity for ACPAs and anti-acetylated peptide antibodies (AAPAs; 45 [12%]); triple positivity for ACPAs, AAPAs, and anti-carbamylated peptide antibodies (151 [42%]); and AMPA negativity (74 [20%]). 19 (5%) patients were in one of the minor autoantibody groups. Of the 233 patients with both antibody data and radiographs of sufficient quality, triple-positive patients had more radiographic progression between baseline and 12 months (estimated mean change in total SvH score 1·8, 95% CI 0·9–2·6, SE 0·4) than did single-positive patients (0·5, 0·1–1·0, 0·2; estimated mean difference in the total change in SvH score 1·2, 95% CI 0·1–2·4, SE 0·5). There was no difference in radiographic progression between single positive patients and AMPA negative patients (estimated mean change in total SvH score 0·7, 95% CI 0·1–1·4, SE 0·3; estimated mean difference in the total change in SvH score −0·2, 95% CI −1·1 to 0·7, SE 0·4). Interpretation: This study suggests that the optimal prediction of future rates of radiographic progression in patients with rheumatoid arthritis will require an assessment of autoantibodies against multiple post-translationally modified proteins or peptides. Funding: The EU FP7 HEALTH programme, the Scottish Translational Medicine Research Collaboration, and the Chief Scientist Office Scotland.

Bibliographic note

Funding Information: This research was funded within the FP7 HEALTH programme under the grant agreement FP7-HEALTH-F2–2012–305549 (EuroTEAM). This work was supported by awards (INF-GU-168) from the Translational Medicine Research Collaboration, a consortium made up of the Universities of Aberdeen, Dundee, Edinburgh, and Glasgow. KR and CDB are funded by the Birmingham National Institute for Health Research Biomedical Research Centre. This work has been supported by the Research into Inflammatory Arthritis Centre Versus Arthritis and the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research. The views expressed in this Article are those of the authors and are not necessarily those of the MRC or Versus Arthritis. The Scottish Early Rheumatoid Arthritis (SERA) inception cohort and biobank was supported by awards (INF-GU-168) from the Translational Medicine Research Collaboration, four associated National Health Service Health Boards (ie, Grampian, Tayside, Lothian, and Greater Glasgow and Clyde), and Pfizer, and from the Chief Scientific Office (Ref ETM-40). We thank Louise Bennett for her assistance with extracting samples from the SERA biobank and Peter Nightingale for his statistical insights. The use of biological and clinical data from the SERA biobank and SERA dataset for the purposes of this study was reviewed by the SERA Access Committee. This Committee has four patient members and they were involved in the development and execution of the SERA Access Policy and reviewed the proposed study, the data and samples required, and the analysis plan. Funding Information: JSN reports personal fees from Janssen Pharmaceuticals and UCB outside the submitted work. HB reports grants from the FP7 HEALTH programme during the conduct of the study, and is an employee of Orgentec Diagnostika GmbH, which manufactures and sells in vitro diagnostics. CDB reports grants from Roche and GSK, and consultancy fees from Pfizer and GSK outside the submitted work. DvdH reports personal fees from AbbVie, Amgen, Astellas, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cyxone, Daichii, Eisai, Elly-Lilly, Galapagos, Gilead, GSK, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, and UCB Pharma outside the submitted work, and is the director of Imaging Rheumatology. IBM reports personal fees from AbbVie, Celgene, Compugen, Galvani, Lilly, Pfizer, and UCB, and grants from AstraZeneca, Celgene, Compugen, Novartis, Roche, and UCB, outside the submitted work. DP reports grants from Pfizer and the Scottish Government's Chief Scientist Office during the conduct of the study. KR reports grants from Abbvie and Pfizer, and personal fees from Abbvie, Pfizer, Sanofi, Lilly, Bristol Myers Squibb, UCB, Janssen, and Roche Chugai outside the submitted work. All other authors declare no competing interests. Funding Information: This research was funded within the FP7 HEALTH programme under the grant agreement FP7-HEALTH-F2?2012?305549 (EuroTEAM). This work was supported by awards (INF-GU-168) from the Translational Medicine Research Collaboration, a consortium made up of the Universities of Aberdeen, Dundee, Edinburgh, and Glasgow. KR and CDB are funded by the Birmingham National Institute for Health Research Biomedical Research Centre. This work has been supported by the Research into Inflammatory Arthritis Centre Versus Arthritis and the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research. The views expressed in this Article are those of the authors and are not necessarily those of the MRC or Versus Arthritis. The Scottish Early Rheumatoid Arthritis (SERA) inception cohort and biobank was supported by awards (INF-GU-168) from the Translational Medicine Research Collaboration, four associated National Health Service Health Boards (ie, Grampian, Tayside, Lothian, and Greater Glasgow and Clyde), and Pfizer, and from the Chief Scientific Office (Ref ETM-40). We thank Louise Bennett for her assistance with extracting samples from the SERA biobank and Peter Nightingale for his statistical insights. The use of biological and clinical data from the SERA biobank and SERA dataset for the purposes of this study was reviewed by the SERA Access Committee. This Committee has four patient members and they were involved in the development and execution of the SERA Access Policy and reviewed the proposed study, the data and samples required, and the analysis plan.

Details

Original languageEnglish
Pages (from-to)e284-e293
JournalThe Lancet Rheumatology
Volume3
Issue number4
Early online date27 Jan 2021
Publication statusPublished - Apr 2021

Keywords

  • Rheumatoid arthritis, acetylated, carbamylated, citrullinated, radiographic progression, ACPA