Article Text

other Versions

PDF
Serum IgG antibodies to peptidylarginine deiminase 4 in rheumatoid arthritis and associations with disease severity
  1. Eirik Hornes Halvorsen (eirikhha{at}medisin.uio.no)
  1. Institute of Immunology, University of Oslo, Norway
    1. Sylvie Pollmann (s.m.pollmann{at}medisin.uio.no)
    1. Institute of Immunology, University of Oslo, Norway
      1. Inge-Margrethe Gilboe (inge-margrethe.gilboe{at}rikshospitalet.no)
      1. Dept of Rheumatology, Rikshospitalet University Hospital, Oslo, Norway
        1. Désirée van der Heijde (d.vanderheijde{at}kpnplanet.nl)
        1. Dept of Rheumatology, Leiden University Medical Center, Leiden, Netherlands
          1. Robert Landewé (rlan{at}sint.azm.nl)
          1. Dept of Rheumatology, University Hospital Maastricht, Maastricht, Netherlands
            1. Sigrid Ødegård (sigrid.odegard{at}diakonsyk.no)
            1. Dept of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
              1. Tore Kristian Kvien (t.k.kvien{at}medisin.uio.no)
              1. Dept of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway
                1. Øyvind Molberg (oyvind.molberg{at}medisin.uio.no)
                1. Institute of Immunology, University of Oslo, Oslo, Norway

                  Abstract

                  Background: Antibodies targeting citrullinated antigens are specific for rheumatoid arthritis (RA). Citrullination is catalyzed by the Peptidylarginine Deiminase (PAD) enzyme family. Critical enzymes are often targeted by disease-specific antibodies in complex immune-mediated diseases. Here, we have tested for auto-antibodies against human recombinant PAD4 (hPAD4) in Caucasian RA patients.

                  Methods: A time-resolved fluorometric immunoassay based on hPAD4 was developed to analyze sera from two RA cohorts (n=237 and n=177), one SLE cohort (n=84) and 148 healthy controls. Simple and multiple analyses were performed to examine possible associations between anti-hPAD4 and disease variables.

                  Results: Raised levels of anti-hPAD4 IgG were found in both RA cohorts compared to the controls, and 23% of the RA patients were anti-hPAD4 IgG positive. Anti-hPAD4 was associated with anti-CCP and RF, as well as increased physical disability. Anti-hPAD4 was also associated with higher longitudinal radiographic damage scores and increased clinical joint pathology, but weaker than anti-CCP. No associations were found between anti-hPAD4 and selected HLA-DRB1 variants.

                  Conclusion: Approximately 23% of Caucasian RA patients have serum IgG antibodies against hPAD4.The presence of serum anti-hPAD4 IgG was in simple analyses associated with a more severe disease phenotype, and the association with physical disability was maintained in multiple analyses.

                  • auto-antibodies
                  • citrullination
                  • peptidylarginine deiminase 4
                  • rheumatoid arthritis

                  Statistics from Altmetric.com

                  • web only appendices 67/3/414

                    Files in this Data Supplement:

                    • view PDF 7 KB - Supplementary figure 1
                      Dose-dependent inhibition of serum anti-hPAD4 IgG binding to solid-phase hPAD4 by incubation with liquid-phase hPAD4. Human albumin was used as a control inhibitor. A pool of five anti-hPAD4 positive RA sera diluted 1:2000 in TBS-T was incubated for 1 hour at 37�C with equal volumes of hPAD4 (▲) or human albumin (▼) in increasing concentrations. Serum pools were then applied to the microtiter plate after the blocking of the plate with 1% BSA.
                    • view PDF 1 KB

                  Request permissions

                  If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.