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Original article
Antibodies against citrullinated peptides are associated with clinical and radiological outcomes in patients with early rheumatoid arthritis: a prospective longitudinal inception cohort study
  1. Antonia Boman1,
  2. Mikael Brink1,
  3. Anders Lundquist2,
  4. Monica Hansson3,
  5. Linda Mathsson-Alm4,5,
  6. Johan Rönnelid6,
  7. Ewa Berglin1,
  8. Rikard Holmdahl7,
  9. Karl Skriner8,
  10. Guy Serre9,
  11. Lars Klareskog3 and
  12. Solbritt Rantapää-Dahlqvist1
  1. 1Department of Public Health and Clinical Medicine/Rheumatology, Umeå University, Umeå, Sweden
  2. 2Department of Statistics, Umeå University, Umeå, Sweden
  3. 3Department of Rheumatology, Karolinska Institutet, Stockholm, Sweden
  4. 4Department of Immunonogy, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  5. 5Thermo Fisher Scientifc, Uppsala, Sweden
  6. 6Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
  7. 7Medical Inflammation Research, Karolinska Institute, Stockholm, Sweden
  8. 8Charité Universitätsmedizin Berlin Campus Charite Mitte, Berlin, Germany
  9. 9Epithelial Differentation and Rheumatoid Autoimmunity Unit, UMRS, University of Toulouse, Toulouse, France
  1. Correspondence to Dr Solbritt Rantapää-Dahlqvist; solbritt.rantapaa.dahlqvist{at}


Introduction Anticitrullinated peptide antibody (ACPA) responses for 22 citrullinated peptides in patients with early rheumatoid arthritis (RA) were analysed and related to radiological and clinical outcome during the first 2 years in a prospective inception cohort.

Methods The ACPA reactivities were assessed in 1022 patients with early RA (symptoms <12 months) using the custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden) in a prospective longitudinal study of observational assessments of Disease Activity Score (DAS28 and its components) and radiology during the first 24 months, accounting for the treatment.

Results Frequency of ACPA reactivities varied between 13.3% and 63.1%. Of the anticyclic citrullinated peptide-2 (anti-CCP2) antibody-negative patients, ACPA reactivities were positive in 32.6%. Smoking, human leucocyte antigen-shared epitope (HLA-SE), anti-CCP2/rheumatoid factor, protein tyrosine phosphatase non-receptor type 22 (1858C/T) and DAS28 were significantly associated with number of ACPA reactivities. The ACPA reactivities modified differently the development of DAS28 over 24 months (identified using trajectories). Anti-Filaggrin307-324, anti-hnRNP (Peptide)-Z1 and anti-F4-CIT-R antibodies anticipated lower DAS28 values (p<0.01–0.05), while positivity for anti-Fibrinogen(Fib)β62-78(74), and anti-Fibα563-583 predicted higher DAS28 (p<0.01 both). Interaction between anti-Fibß36-52, anti-Pept-5 and anti-Bla-26 antibodies, respectively, and DAS28 during 24 months decreased significantly the DAS28 values (p<0.01–0.05). Corticosteroids and biologicals were related to DAS28-area under the curve and Larsen score 24 months. Anti-vimentin2-17 antibodies remained significantly associated with Larsen score at baseline and 24 months, respectively, and radiological progression, besides biologicals at 24 months adjusted for sex and age.

Conclusions Several ACPA reactivities modified significantly the DAS28 development during the first 24 months and were significantly associated with Larsen score at baseline, 24 months and radiological progression.

  • Early rheumatoid arthritis
  • anti-citrullinated protein/peptide antibodies (ACPA)
  • multiplex antibody analyses
  • Larsen score
  • 28-joint disease activity score (DAS28)

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  • Contributors AB, JR, LK and SR-D made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data; MH, LM-A and EB have been involved in analysing the data of the samples and of the patients. All authors have been involved in drafting the manuscript or revising it critically for important intellectual content; AB, MB, AL and SR-D have been involved in analysing and calculating the data; RH, KS and GS have provided the antigens of the peptides. All authors have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors read and approved the final manuscript.

  • Funding This study was supported by grants from the Swedish Research Council (K2013-52X-2030707-3 and Dnr:2018-02551), King Gustaf V’s 80-Year Fund, King Gustaf V’s and Queen Victoria’s Fund, the Swedish Rheumatism Association, Umeå University, Umeå, Sweden.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval The patients gave their written informed consent and the Regional Ethics Committee at Umeå University Hospital approved the study.

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

  • Data availability statement Data are available on reasonable request. All data relevant to the study are included in the article or uploaded as supplementary information.