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

Abstract

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.

• Authors: E H Halvorsen, E A Haavardsholm, S Pollmann, A Boonen, D van der Heijde, T K Kvien, Ø Molberg
• Journal: Annals of the rheumatic diseases (Ann Rheum Dis) Vol. 68 Issue 2 Pg. 249-52 (Feb 2009) ISSN: 1468-2060 [Electronic] England
• PMID: 18723564 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents
• Autoantibodies
• Immunoglobulin G
• Receptors, Tumor Necrosis Factor
• Tumor Necrosis Factor-alpha
• Infliximab
• Hydrolases
• PADI4 protein, human
• Protein-Arginine Deiminase Type 4
• Protein-Arginine Deiminases
• Adalimumab
• Etanercept

Topics

• Adalimumab
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antirheumatic Agents (therapeutic use)
• Arthritis, Rheumatoid (diagnostic imaging, drug therapy, immunology)
• Autoantibodies (blood)
• Disease Progression
• Etanercept
• Female
• Humans
• Hydrolases (immunology)
• Immunoglobulin G (blood, therapeutic use)
• Infliximab
• Male
• Middle Aged
• Prognosis
• Protein-Arginine Deiminase Type 4
• Protein-Arginine Deiminases
• Radiography
• Receptors, Tumor Necrosis Factor (therapeutic use)
• Severity of Illness Index
• Treatment Outcome
• Tumor Necrosis Factor-alpha (antagonists & inhibitors)