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Reversible changes in serum immunoglobulin galactosylation during the immune response and treatment of inflammatory auto-immune arthritis
  1. Katrien Van Beneden (katrien.vanbeneden{at}ugent.be)
  1. Ghent University, Belgium
    1. Ken Coppieters (ken{at}liai.org)
    1. Ghent University, Belgium
      1. Wouter Laroy (wouter.laroy{at}pronota.com)
      1. Flanders Interuniversity Institute for Biotechnology and Ghent University, Belgium
        1. Filip De Keyser (filip.dekeyser{at}ugent.be)
        1. Ghent University, Belgium
          1. Ilse E. Hoffman (ilse.hoffman{at}skynet.be)
          1. Ghent University, Belgium
            1. Filip Van den Bosch (filip.vandenbosch{at}ugent.be)
            1. Ghent University, Belgium
              1. Bert Vander Cruyssen (bert.vandercruyssen{at}ugent.be)
              1. Ghent University, Belgium
                1. Michael Drennan (michael.drennan{at}ugent.be)
                1. Ghent University, Belgium
                  1. Peggy Jacques (peggy.jacques{at}ugent.be)
                  1. Ghent University, Belgium
                    1. Pieter Rottiers (pieter.rottiers{at}actogenix.com)
                    1. ActoGeniX NV, Belgium
                      1. Gust Verbruggen (gust.verbruggen{at}ugent.be)
                      1. Ghent University, Belgium
                        1. Roland Contreras (roland.contreras{at}ugent.be)
                        1. Flanders Interuniversity Institute for Biotechnology and Ghent University, Belgium
                          1. Nico Callewaert (nico.callewaert{at}ugent.be)
                          1. Flanders Interuniversity Institute for Biotechnology and Ghent University, Belgium
                            1. Dirk Elewaut (dirk.elewaut{at}ugent.be)
                            1. Ghent University, Belgium

                              Abstract

                              Objectives: In this study we used the improved DNA-sequencer aided FACE (DSA-FACE) technology to monitor the changes in the galactosylation status of serum immunoglobulins during the immune response and therapy of auto-immune arthritis.

                              Methods: Collagen-induced arthritis (CIA) was induced in susceptible DBA/1 mice and the undergalactosylation status (UGS) of serum immunoglobulins was determined using the improved DSA-FACE technology. Prophylactic intravenous tolerization with type-II collagen as well as semi-therapeutic treatment with Dexamethasone (DEX) were performed, and UGS was analyzed. Next, we studied the serum immunoglobulin glycosylation profile in both rheumatoid arthritis (RA) and spondyloarthropathy (SpA) patients, and followed changes in the UGS scores during anti-TNFα therapy.

                              Results: In the longitudinal CIA study, the undergalactosylation state of immunoglobulins was found to be significantly correlated with the clinical arthritis scores. Upon collagen-specific tolerization as well as glucocorticoid semi-therapeutic treatment, improvement of the clinical arthritis scores correlated with decreased levels of UGS. We also demonstrated that withdrawal of DEX was associated with an increased UGS score. Interestingly, reversibility in the UGS was also shown during treatment of both RA and SpA patients with anti-TNFα.

                              Conclusions: These findings demonstrate that the UGS of serum immunoglobulins changes during the disease course of CIA and that this UGS is inhibited by antigen-specific and antigen-independent treatment procedures. The observation that Ig galactosylation is a reversible process is also documented during treatment of both RA and SpA patients with anti-TNFα.

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