Serum IgG antibodies to peptidylarginine deiminase 4 predict radiographic progression in patients with rheumatoid arthritis treated with tumour necrosis factor-α blocking agents

Background: Peptidylarginine deiminase 4 (PAD4) may generate epitopes targeted by anticitrullinated protein antibodies in rheumatoid arthritis (RA). A subset of patients with RA has serum autoantibodies to human recombinant PAD4 (hPAD4). Here, we assessed whether anti-hPAD4 status in RA predicted disease outcome after antitumour necrosis factor (anti-TNF)-alpha therapy. Methods: We analysed RA sera obtained at baseline (n = 40) and after 1 year on anti-TNF-alpha therapy (n = 33) for anti-hPAD4 IgG. Association analyses between baseline anti-hPAD status and disease progression were performed. Results: We found that 17 of 40 patients (42.5%) were serum anti-hPAD4 positive at baseline, and the anti-hPAD4 IgG levels were stable over 1 year on anti-TNF-alpha therapy. At baseline, there were indications that anti-hPAD4 positive patients had more severe disease than the negative patients. After 1 year on anti-TNF-alpha therapy, the anti-hPAD4 positive patients displayed a persistently elevated disease activity score using 28 joint counts score and increased progression in the van der Heijde-modified Sharp erosion score. Accordingly, more anti-hPAD4 positive than negative patients presented an increase in van der Heijde-modified Sharp erosion scores >0 over 1 year. Conclusions: Anti-hPAD4 IgG can be detected in a subset of RA sera and the levels are stable after initiation of anti-TNF-alpha therapy. Serum anti-hPAD4 may predict persistent disease activity and radiographic progression in patients with RA receiving anti-TNF-alpha therapy.