Academisch Medisch Centrum Universiteit van Amsterdam

Immunopathology of chronic inflammatory arthritis

NAME: Baeten Dominique, MD, PhD
BIRTH: 12/12/1970

EDUCATION/TRAINING

MD, Ghent University, Belgium
PhD, Ghent University, Belgium
Rheumatologist, Dept of Health, Belgium
MBA, Nantes Business School, France

A. Positions
• Senior Clinical Investigator of the Fund for Scientific Research-Flanders (FWO-Vlaanderen), Belgium, from 01/10/2002 to 31/12/05.
• Assistant Professor, Internal Medicine, Ghent University, Belgium, since 01/10/03.
• Visiting Scientist in transplantation immunology, INSERM U643, Nantes, France, from 1/10/2003 to 30/9/2004
• Visiting Scientist in neuroimmunology, Harvard Medical School, Boston, USA, from 1/10/2004 to 30/9/2005
• Associate Professor in the Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands, since 01/01/06.
• Director of the FOCIS Center of Excellence of the University of Amsterdam, from May 2006.

B. Selected peer-reviewed publications
1. Baeten D., Peene I., Union A., Meheus L., Sebbag M., Serre G., Veys EM., De Keyser F. Specific presence of intracellular citrullinated proteins in rheumatoid arthritis synovium: relevance to antifilaggrin autoantibodies. Arthritis Rheum 2001;44:2255-2262. (IF 7.414)
2. Baeten D., Steenbakkers PGA., Rijnders AMW., Boots A.., Veys EM., De Keyser F. Specific presence of MHC/HC gp-39 complexes in rheumatoid arthritis synovitis as a new and independent histological marker. Arthritis Rheum 2004;50:444-51 (IF 7.414).
3. De Rycke L., Nicholas AP., Cantaert T., Kruithof E., Echols JD., Vandekerckhove B., Veys EM., De Keyser F., Baeten D. Synovial intracellular citrullinated proteins colocalizing with peptidyl arginine deiminase type 2 as pathophysiologically relevant antigenic determinants of rheumatoid arthritis specific humoral autoimmunity. Arthritis Rheum 2005;52:2323-2330 (IF 7.421).
4. Bettelli E. and Baeten D. (equal contribution), Sobel RA, Kuchroo VK. Myelin oligodendrocyte glycoprotein (MOG) specific T and B cells cooperate to induce a severe form of Devic’s like disease in mice. J Clin Invest 2006;116:2393-402 (IF 15053).
5. Cantaert T., De Rycke L., Bongartz T., Matteson E., Tak PP., Nicholas AP., Baeten D. Citrullinated proteins in rheumatoid arthritis: crucial … but not sufficient! Arthritis Rheum 2006;54:3381-9 (impact factor 7.421).
6. Cantaert T., Kolln J., Timmer T. Van der Pouw-Kraan T., Vandooren B., Thurlings R., Canete J., Catrina AI., Out T., Verweij C., Zhang Y., Tak PP., Baeten D. Humoral autoimmunity in the rheumatoid joint is not driven by ectopic lymphoid neogenesis. J Immunol 2008;181:785-94 (impact factor 6,068).

C. Research Programs:

1. Curing autoimmune diseases. A translational approach to autoimmune diseases in the post-genomic area using inflammatory arthritis and myositis as prototype and learning examples. Integrated Project of the Sixth Framework Program of the European Union. 2006. Co-investigator.
2. Immunopathology of chronic autoimmune arthritis and opportunities for immunomodulation. Academic Medical Center Fellowship. 2006. Principal Investigator.
3. Characterization and immunomodulation of B lymphocyte responses in human spondyloarthritis. Dana Foundation Program in Human Immunology. 2006. Principal Investigator.
4. Defective regulation of cytokine signaling in macrophage-mediated inflammation and excessive tissue repair in human spondyloarthritis. NWO Vernieuwingsimpuls ‘Vidi’ Grant. 2007. Principal Investigator.
5. Autoantigen-specific B cells in rheumatoid arthritis. American College of Rheumatology ‘Within Our Reach’ Grant. 2007. Principal Investigator.
6. Cytokine signalling in macrophage-mediated inflammation in human spondyloarthritis. Reumafonds grant. 2008. Principal Investigator.
7. Immunomodulation of B cell responses by TNF blockade. Reumafonds grant. 2008. Principal Investigator.

 

The research of our team if focused on 2 aspects of the immunopathogenesis of chronic inflammatory arthritis: the relation between macrophage-mediated inflammation and tissue repair in spondyloarthritis (SpA) and the role of B cells in different types of arthritis.

In 2006, we have studied in detail several aspects of tissue damage and repair in SpA. We have demonstrated that the RANKL-RANK-OPG system can not explain the differences in tissue damage pattern between SpA and rheurmatoid arthritis (RA) and that the expression of this system is largely independent of local and systemic inflammation. We have also clear indications that other cells beside activated T lymphocytes and fibroblast-like synoviocytes are able to express RANKL and thus promote osteoclastogenesis.

We also showed that fibroblast-like synoviocytes can express cadherin-11 in different types of joint pathology. This expression is not constitutive but regulated by inflammation in vivo and in vitro. The TNF alpha mediated upregulation acts via Erk and p38 signalling and can be reversed by treatment in vivo.

Finally, we have demonstrated that chondrocyte anabolism is severely suppressed by inflammation, is differentially regulated between SpA and RA, and can be restored by systemic blockade of proinflammatory cytokines in vivo.

As to B cells, we have demonstrated that ectopic lymphogenesis occurs in different types of chronic arthritis, is related to the severity rather than the type of inflammation, and does not contribute to oligoclonal B cell expansion and/or autoantibody production.

We have also demonstrated that anti-nuclear antibodies can be induced by TNFalpha blockade in RA as well as in SpA and that this induction is related to apoptosis and release of nucleosomes on the one hand. Other factors such as BAFF, APRIL, and type I IFN do not appear to play a role.

Theme: Infection and Immunity