title: Anti-peptidyl-arginine deaminase 3 (PAD3) antibodies as a promising marker to measure joint damage in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Recently, antibodies directed against peptidyl arginine deiminase 3 and 4 (anti-PAD3/PAD4 antibodies), calcium-dependent enzymes that catalyze the conversion from arginine to citrulline, have been described. Furthermore, antibodies that cross-react between PAD3 and PAD4 cause increased PAD4 activity and consequently correlate with joint damage. This study analyzes the correlation of anti-PAD3 antibodies with joint damage.
  
  
  METHODS
  To validate the novel chemiluminescent immunoassay (CIA) for the detection of anti-PAD3 antibodies, 20 samples were tested by CIA and by immunoprecipitation (IP). Next, 39 RA patients with available joint erosion score (JES), Total Sharp Score (TSS) and Joint Space Narrowing Score (JSNS) were tested for anti-CCP (using different methods) and anti-PAD3 antibodies by CIA.
  
  
  RESULTS
  Excellent correlation was observed between the CIA and IP for the detection of anti-PAD3 antibodies (rho=0.85, p<0.0001). The median JES of our 39 patients was 14.1 with a standard deviation of 11.5. Anti-PAD3 antibody levels (rho=0.39, 95% CI=0.1-0.6; p=0.0149) were correlated with JES. No correlation was found with TSS and JSNS. In this cohort, ACPA measured using different anti-CCP assays did not correlate with the JES.
  
  
  CONCLUSIONS
  In our cohort, anti-PAD3 antibodies correlate with joint erosion score. Therefore, anti-PAD3 antibodies might represent promising markers to predict joint damage in RA patients.
authors.affiliation: Inova Diagnostics, Inc., San Diego, CA, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Seaman
authors.affiliation: Rheumatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Erika
authors.initials: E
authors.lastname: Darrah
authors.affiliation: Immunology and Allergology Laboratory Unit, Ospedale S. Giovanni di Dio, Florence, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Infantino
authors.affiliation: Rheumatology Unit, Ospedale S. Giovanni di Dio, Florence, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Meacci
authors.affiliation: Immunology and Allergology Laboratory Unit, Ospedale S. Giovanni di Dio, Florence, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Manfredi
authors.affiliation: Rheumatology Unit, Ospedale S. Giovanni di Dio, Florence, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Benucci
authors.affiliation: Inova Diagnostics, Inc., San Diego, CA, USA. Electronic address: mmahler@inovadx.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Mahler
mesh_terms: D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D000076342:Protein-Arginine Deiminases
chemical_list: D001323:Autoantibodies; D006867:Hydrolases; D000076342:Protein-Arginine Deiminases
keywords: Autoantibodies; CCP; Citrullinated cyclic peptide; PAD; Peptidyl arginine deiminase; RA; Rheumatoid arthritis