Volume 7 Supplement 1

25th European Workshop for Rheumatology Research

Open Access

Functional regulatory immune responses against human cartilage glycoprotein-39 in health versus proinflammatory responses in rheumatoid arthritis

  • JHM van Bilsen1,
  • H van Dongen1,
  • LR Lard1,
  • EIH van der Voort1,
  • DG Elferink2,
  • AM Bakker1,
  • AMM Miltenburg3,
  • TWJ Huizinga1,
  • RRP de Vries2 and
  • REM Toes1
Arthritis Research & Therapy20057(Suppl 1):P37

DOI: 10.1186/ar1558

Received: 11 January 2005

Published: 17 February 2005

The class of immune response against autoantigens could profoundly influence the onset and/or outcome of autoimmune diseases. Until now, there is only limited information on the antigen-specific balance between proinflammatory and regulatory responses in humans. Here we analyzed the natural immune response against a candidate autoantigen in rheumatoid arthritis, Human Cartilage gp-39 (HC gp-39).

Peripheral blood mononuclear cells from healthy individuals reacted against HC gp-39 with the production of IL-10, but not interferon gamma (Fig. 1). Ex vivo assays indicated that the naturally occurring HC gp-39-specific immune response in bulk is powerful enough to suppress antigen-specific recall responses, demonstrating that, rather than being unresponsive, the HC gp-39-directed immune response in healthy individuals shows a strong bias towards a regulatory phenotype. Moreover, CD4+ T-cell lines directed against HC gp-39 expressed CD25, GITR and Foxp3 molecules and were capable of suppressing antigen-specific T-cell responses. Cell–cell contact was required for this suppression. As opposed to healthy individuals, the HC gp-39-directed immune response in 50% of patients with rheumatoid arthritis exhibits polarization towards a proinflammatory Th1 phenotype and is significantly less powerful in suppressing antigen-specific recall responses.
Figure 1

Human Cartilage gp-39 (HC gp-39)-specific immune reactivity in healthy donors. (a) Peripheral blood mononuclear cells from healthy donors (n = 31) react against HC gp-39 by production of IL-10 but not interferon gamma (IFN-γ). (b) 'Control' recall antigen-induced responses are dominated by IFN-γ production.

Together these findings indicate that the presence of HC gp-39-specific immune responses in healthy individuals may have an inhibitory effect on inflammatory responses in areas where HC gp-39 is present. Furthermore, these data indicate that the class of HC gp-39-directed immune response in RA patients has shifted from an anti-inflammatory towards a proinflammatory phenotype.



This work was supported by The Dutch Arthritis Association. REMT is supported by a Vidi Grant from the Netherlands Organization for Scientific Research. HvD and LRL are supported by The Netherlands Organization for Health Research and Development.

Authors’ Affiliations

Department of Rheumatology, Leiden University Medical Center
Department of Immunoheamatology and Blood Transfusion, Leiden University Center
NV Organon


© BioMed Central Ltd 2005