Association of anti-peptidyl arginine deiminase antibodies with radiographic severity of rheumatoid arthritis in African Americans

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.