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Serum IgG antibodies to peptidylarginine deiminase 4 predict radiographic progression in patients with rheumatoid arthritis treated with tumour necrosis factor-α blocking agents
  1. E H Halvorsen1,
  2. E A Haavardsholm2,
  3. S Pollmann1,
  4. A Boonen3,
  5. D van der Heijde2,4,
  6. T K Kvien2,
  7. Ø Molberg1,5
  1. 1
    Institute of Immunology, Faculty of Medicine, University of Oslo and Rikshospitalet University Hospital, Oslo, Norway
  2. 2
    Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
  3. 3
    Department of Rheumatology, University Hospital Maastricht, Maastricht, The Netherlands
  4. 4
    Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands
  5. 5
    Department of Rheumatology, Rikshospitalet University Hospital, Oslo, Norway
  1. Eirik Hornes Halvorsen, Institute of Immunology, University of Oslo, Rikshospitalet University Hospital, Oslo, Norway; eirikhha{at}


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)-α therapy.

Methods: We analysed RA sera obtained at baseline (n = 40) and after 1 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 1 year on anti-TNF-α 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-α 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-α therapy. Serum anti-hPAD4 may predict persistent disease activity and radiographic progression in patients with RA receiving anti-TNF-α therapy.

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  • Competing interests: Hans Bijlsma was the Handling Editor for this article.

  • Funding: This work was supported by grants from Rikshospitalet University Hospital and the Research Council of Norway. EHH is financed by a PhD stipend from the University of Oslo.

  • ▸ Additional supplemental tables 1 and 2 are published online only at

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