title: Association of anti-peptidyl arginine deiminase antibodies with radiographic severity of rheumatoid arthritis in African Americans.
abstract: Evidence suggests that the presence of peptidyl arginine deiminase type 4 (PAD4) antibodies is associated with radiographic-severity rheumatoid arthritis (RA) among Caucasian patients. The presence of anti-PAD4 antibodies that were cross-reactivity against PAD3 was associated with more aggressive erosive disease (compared with the presence of anti-PAD4 antibodies without anti-PAD3 crossreactivity) in Caucasian RA patients. The objectives of this study were to determine the prevalence of serum anti-PAD4 and anti-PAD4/PAD3 cross-reactive autoantibodies in African Americans with RA and whether these antibodies associate with radiographic severity and radiographic progression.
  
  
  
  Serum anti-PAD4 and anti-PAD4/PAD3 antibodies were measured by immunoprecipitation, and the temporal trends in titers were analyzed. We compared total radiographic scores among anti-PAD4-positive, anti-PAD4/PAD3-positive, and anti-PAD4-negative patients and used a zero-inflated negative binomial model to determine associations between radiographic severity and antibody status. Logistic regression was used to analyze radiographic progression.
  
  
  
  Of 192 African-American patients with RA, 73 % were anti-citrullinated peptide/protein antibody (ACPA)-positive, 46 out of 192 (24 %) of whom had serum anti-PAD4 antibodies. Median (interquartile range) total Sharp van der Heijde radiographic scores were 2 (1-97.5) in ACPA-positive patients and 0 (0-3) in ACPA-negative patients (P < 0.001). Of the 46 anti-PAD4-positive patients, 20 had anti-PAD4 antibodies that cross-reacted with PAD3. In patients with early RA, anti-PAD4 and anti-PAD4/PAD3 antibody titers increased over time (P = 0.006, P = 0.001, respectively). Median (interquartile range) total radiographic scores were higher for anti-PAD4-positive than for anti-PAD4-negative patients (3 (1-115) versus 2 (0-11), respectively; P = 0.005). Median (interquartile range) total radiographic score for anti-PAD4/PAD3-positive patients was 76 (3-117) (P < 0.001) versus anti-PAD4-negative patients. Only anti-PAD4/PAD3 antibodies associated with radiographic severity (incidence rate ratio = 2.81; 95 % confidence interval 1.23, 6.43).
  
  
  
  This analysis suggests that autoantibodies against PAD4 and PAD3 proteins may serve as biomarkers for identifying African-American patients with RA and higher radiographic severity.
authors: University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 850, Birmingham, AL, 35294-3408, USA. inavarro@uabmc.edu.
authors: Iris
authors: 0000-0001-6963-427X
authors: I
authors: Navarro-Millán
authors: Division of Rheumatology, The Johns Hopkins University, Baltimore, MD, USA.
authors: Erika
authors: E
authors: Darrah
authors: University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 850, Birmingham, AL, 35294-3408, USA.
authors: Andrew O
authors: AO
authors: Westfall
authors: VA Nebraska-Western Iowa Health Care System and University of Nebraska Medical Center, Omaha, NE, USA.
authors: Ted R
authors: TR
authors: Mikuls
authors: University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 850, Birmingham, AL, 35294-3408, USA.
authors: Richard J
authors: RJ
authors: Reynolds
authors: University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 850, Birmingham, AL, 35294-3408, USA.
authors: Maria I
authors: MI
authors: Danila
authors: University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 850, Birmingham, AL, 35294-3408, USA.
authors: Jeffrey R
authors: JR
authors: Curtis
authors: Division of Rheumatology, The Johns Hopkins University, Baltimore, MD, USA.
authors: Antony
authors: A
authors: Rosen
authors: University of Alabama at Birmingham, 510 20th Street South, Faculty Office Tower 850, Birmingham, AL, 35294-3408, USA.
authors: S Louis
authors: SL
authors: Bridges
mesh_terms: D000328:Adult; D001741:Black or African American; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging / Q000276:immunology / Q000473:pathology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003429:Cross Reactions; D018450:Disease Progression; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000276:immunology*; D047468:Immunoprecipitation; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
keywords: African American; Anti-PAD4; Radiographic severity; Rheumatoid arthritis