Background: Peptidylarginine Deiminase 4 (PAD4) may generate epitopes targeted by anti-citrullinated protein antibodies in rheumatoid arthritis (RA). A subset of RA patients has serum autoantibodies to human recombinant PAD4 (hPAD4). Here, we assessed whether anti-hPAD4 status in RA predicted disease outcome after anti-TNF-α therapy.
Methods: We analyzed RA sera obtained at baseline (n=40) and after one year on anti-TNF-α 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 one year on anti-TNF-α therapy. At baseline, there were indications that the anti-hPAD4 positive patients had more severe disease than the negative patients. After one year on anti-TNF-α therapy, the anti-hPAD4 positive patients displayed persistently elevated DAS28 score and increased progression in the vdHSharp erosion score. Accordingly, more anti-hPAD4 positive than negative patients presented an increase in vdHSharp erosion scores >0 over one year.
Conclusion: Anti-hPAD4 IgG can be detected in a subset of RA sera and the levels are stable after initiation of anti-TNF-α therapy. Serum anti-hPAD4 may predict persistent disease activity and radiographic progression in RA patients receiving anti-TNF-α therapy.