RESEARCH - Serum IgG antibodies to PAD4 predict radiographic progression in RA patients treated with anti-TNF-blocking agents

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Ann Rheum Dis. Published Online First: 22 August 2008.

doi:10.1136/ard.2008.094490

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Concise Report

Serum IgG antibodies to Peptidylarginine Deiminase 4 predict

radiographic progression in rheumatoid arthritis patients treated with

TNF- blocking agents

Eirik Hornes Halvorsen 1*, Espen A Haavardsholm 2, Sylvie Pollmann 1,

Annelies Boonen 3, Désirée van der Heijde 4, Tore K Kvien 2 and yvind

Molberg 5

1 Institute of Immunology, University of Oslo, Norway

2 Department of Rheumatology, Diakonhjemmet Hospital, Norway

3 Department of Rheumatology, University Hospital Maastricht, Netherlands

4 Department of Rheumatology, Leiden University Medical Center, Netherlands

5 Department of Rheumatology, Rikshospitalet University Hospital, Norway

Abstract

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- therapy.

Methods: We analyzed RA sera obtained at baseline (n=40) and after one

year on anti-TNF- 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- 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- 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- therapy. Serum

anti-hPAD4 may predict persistent disease activity and radiographic

progression in RA patients receiving anti-TNF- therapy.

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http://ard.bmj.com/cgi/content/abstract/ard.2008.094490v1?papetoc

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