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Serum IgG antibodies to Peptidylarginine Deiminase 4 predict radiographic progression in rheumatoid arthritis patients treated with TNF-α blocking agents
  1. Eirik Hornes Halvorsen (eirikhha{at}
  1. Institute of Immunology, University of Oslo, Norway
    1. Espen A Haavardsholm (e.a.haavardsholm{at}
    1. Department of Rheumatology, Diakonhjemmet Hospital, Norway
      1. Sylvie Pollmann (sylvie.pollmann{at}
      1. Institute of Immunology, University of Oslo, Norway
        1. Annelies Boonen (a.boonen{at}
        1. Department of Rheumatology, University Hospital Maastricht, Netherlands
          1. Désirée van der Heijde (d.vanderheijde{at}
          1. Department of Rheumatology, Leiden University Medical Center, Netherlands
            1. Tore K Kvien (t.k.kvien{at}
            1. Department of Rheumatology, Diakonhjemmet Hospital, Norway
              1. Øyvind Molberg (oyvind.molberg{at}
              1. Department of Rheumatology, Rikshospitalet University Hospital, Norway


                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.

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