Autoantibodies to peptidylarginine deiminase 2 are associated with less severe disease in rheumatoid arthritis

Erika Darrah, Jon T. Giles, Ryan L. Davis, Pooja Naik, Hong Wang, Maximilian F. Konig, Laura C. Cappelli, Clifton O. Bingham, Sonye K. Danoff, Felipe Andrade

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Objective: Peptidylarginine deiminases (PAD) 2 and 4 are key enzymes in rheumatoid arthritis (RA) pathogenesis due to their ability to generate the protein targets of anti-citrullinated protein antibodies (ACPA). Anti-PAD4 antibodies that cross-react with PAD3 (anti-PAD3/4) have been identified and are associated with severe joint and lung disease. Here, we examined whether anti-PAD2 antibodies were present in patients with RA and defined their clinical significance. Patients and Methods: A PAD2 ELISA was established to screen for anti-PAD2 IgG in sera from RA patients from a prospective observational cohort study (n = 184) and healthy controls (n = 100). RA patient characteristics were compared according to anti-PAD2 antibody status. Multivariable models were constructed to explore the independent associations of anti-PAD2 antibodies with clinical variables. Results: Anti-PAD2 antibodies were found in 18.5% of RA patients and 3% of healthy controls (p < 0.001). Among RA patients, anti-PAD2 antibodies were not associated with traditional genetic or serologic RA risk factors, including HLA-DRβ1 shared epitope alleles, ACPA, rheumatoid factor (RF), or anti-PAD3/4 antibodies. In addition, antibodies to PAD2 were associated with fewer swollen joints, a lower prevalence of interstitial lung disease, and less progression of joint damage. In subset analyses in which patients were stratified by the baseline presence of ACPA/RF or anti-PAD3/4 antibodies, anti-PAD2 antibodies provided additional value in identifying patients with the least progressive joint disease. Conclusions: Anti-PAD2 antibodies represent a novel serologic marker in RA that identifies a genetically and clinically unique subset of patients with less severe joint and lung disease.

Original languageEnglish (US)
Article number2696
JournalFrontiers in immunology
Issue numberNOV
StatePublished - Nov 20 2018


  • Autoantibodies
  • Autoimmunity
  • Disease activity
  • Interstitial lung disease
  • Peptidylarginine deiminase
  • Rheumatoid arthritis
  • Shared epitope
  • Sharp score

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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