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Anti-carbamylated proteins antibody repertoire in rheumatoid arthritis: evidence of a new autoantibody linked to interstitial lung disease
  1. Raul Castellanos-Moreira1,
  2. Sebastian Cruz Rodríguez-García1,
  3. Maria Jose Gomara2,
  4. Virginia Ruiz-Esquide1,
  5. Andrea Cuervo1,
  6. Ivette Casafont-Solé3,
  7. Julio Ramírez1,
  8. Susana Holgado3,
  9. Jose A Gómez-Puerta1,
  10. Juan D Cañete1,
  11. Isabel Haro2,
  12. Raimon Sanmarti1
  1. 1 Rheumatology Department, Arthritis Unit, Hospital Clinic de Barcelona, Barcelona, Spain
  2. 2 Consejo Superior de Investigaciones Científicas, Unit of Synthesis and Biomedical Applications of Peptides, CSIC-IQAC, Barcelona, Spain
  3. 3 Rheumatology Department, Hospital Germans Trias i Pujol, Badalona, Spain
  1. Correspondence to Dr Raimon Sanmarti, Arthritis Unit, Rheumatology Department, Hospital Clinic de Barcelona, Barcelona 08036, Spain; sanmarti{at}


Objective To analyse the association between anti-carbamylated protein antibodies (Anti-CarP) and interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients.

Methods Cross-sectional study including RA patients fulfilling the 2010 ACR/EULAR criteria. The main population comprised two groups: (1) RA patients diagnosed with RA-ILD (RA-ILD group); (2) RA patients without ILD (non-ILD RA group). Non-ILD RA patients in whom ILD was suspected underwent a diagnostic work-up and, if ILD was diagnosed, were switched to the RA-ILD group. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. An independent replication sample was also obtained. Three Anti-CarP IgG autoantibodies against fetal calf serum (Anti-FCS), fibrinogen (Anti-Fib) and chimeric fibrine/filagrine homocitrullinated peptide (Anti-CFFHP) and one Anti-CarP IgA against FCS (Anti-FCS-IgA) were determined by home-made ELISA. Associations between Anti-CarP and ILD were analysed using multivariable logistic regression adjusted by smoking, sex, age, RA disease duration, rheumatoid factor and anticitrullinated protein antibodies.

Results We enrolled 179 patients: 37 (21%) were finally diagnosed with RA-ILD. Anti-CarP specificities were more frequent in RA-ILD patients (Anti-FCS 70% vs 43%; Anti-Fib 73% vs 51%; Anti-CFFHP 38% vs 19%; Anti-CarP-IgA 51% vs 20%, p<0.05 for all comparisons). Serum titers of Anti-CarP were significantly higher in RA-ILD patients. Anti-CarP specificities showed a robust effect towards increasing the odds of ILD in the multivariate analysis (Anti-FCS (OR: 3.42; 95% CI: 1.13 to 10.40), Anti-Fib (OR: 2.85; 95% CI: 0.83 to 9.70), Anti-CFFHP (OR: 3.11; 95% CI: 1.06 to 9.14) and Anti-FCS-IgA (OR: 4.30; 95% CI: 1.41 to 13.04)). Similar findings were observed in the replication sample.

Conclusions Anti-CarP were strongly associated with ILD. The role of homocitrullination in RA-ILD merits further investigation.

  • rheumatoid arthritis
  • smoking
  • autoantibodies
  • pulmonary fibrosis
  • anti-CCP

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  • Handling editor Josef S Smolen

  • Twitter @raul_cast_morei, @sdlcrodriguez

  • RC-M and SCR-G contributed equally.

  • Correction notice This article has been corrected since it published Online First. The second affiliation has been updated.

  • Contributors RC-M, SCR-G, IH and RS contributed to the conception and study design. RC-M, JR, JG-P, VR-E, IC-S, SH and JDC contributed to data collection. RC-M, SCR-G and MJG analysed the data. RC-M, SCR-G, VR-E and IH contributed to interpretation of the data. RC-M, SCR-G and RS wrote the first version of the manuscript and AC, JR, JG-P, JDC, VR-E, IC-S, SH and IH revised it critically. All authors read and approved the final manuscript.

  • Funding Financial support from the Hospital Clinic of Barcelona, Research, Innovation and Education Department (Grant # 37 933 to RC-M and the Spanish Ministry of Economy, Industry and Competitiveness and the European Regional Development Fund (Grant # RTI2018-094120-B-I00 to IH).

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Ethics approval The study was conducted in accordance with the Declaration of Helsinki and was approved by the Hospital Clinic of Barcelona Ethics Committee (approval number 2017/0679).

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

  • Data availability statement Data are available upon reasonable request. Data is available upon reasonable request, all data relevant to the study are included in the article.