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Afgeronde projecten

Welke projecten zijn de laatste jaren afgerond?

U vindt hier een korte Engelse beschrijving van de onderzoeksprojecten die zijn afgerond in 2011.

Oudere afgeronde projecten vindt u in het archief.

2011

Identification of novel lipid mediators in the joints of arthritic patients by metabolomics
Projectleader: Dr.A. Ioan-Facsinay
University: LUMC Leiden
E-mail: A.Ioan@lumc.nl

The aim of this study was to identify and measure lipid mediators present in synovial fluid and fat/adipocyte-conditioned medium from RA en OÁ patients and to study differences between lean and obese individuals.

The researchers have identified several lipid classes in SF and ACM of arthritis patients. Some fatty acids were higher in obese/overweight than lean OA patients. Also lipids that have been associated with the pathogenes of osteoarthritis were detected in different concentrations in SF and FCM.

Follow-up research will be focused on investigating the immunomodulatory function of the identified lipids and identification of novel lipid mediators in OA en RA.

Lymph nodes: the primary site of initiation of RA-
specific autoimmunity?
Projectleader: prof. dr. P.P. Tak
University: AMC Amsterdam
E-mail: p.p.tak@amc.uva.nl

In this study the researchers investigated the differences in cellular composition and functional aspects of lymph nodes in different phases of RA. They investigated lymph nodes in early arthritis patients and compared this with autoantibody positive individuals without arthritis (pre-clinical RA). The researchers found that T- en B-cell HECs can be detected in synovial tissue and lymph nodes of early RA patients. Up to 40% of the HECs in the synovial tissue are also found in the lymph node.

These results may be explained by circulation of clones between the synovium and the lymph node and suggest local retention of clones in the synovial tissue. The results also suggest increased CD8+ T cell activation within lymph nodes of early arthritis patients as well as in autoantibody positive individuals who are at risk of developing RA.

The role of dendritic cell subsets in arthritis: an in vivo study
Projectleader: prof. dr. P.P.Tak
University: AMC Amsterdam
E-mail: p.p.tak@amc.uva.nl

The unraveling of the functional roles of two main DC subsets in the pathogenesis of arthritis was the focus of this researchproject. Animal experiments show that there is an important role for these subsets in arthritis. But key experiments must pinpoint there exact contribution in arthritis and at which timepoint their contribution is crucial. When that information is available it will be time to develop gene-based or small cell-permeable peptides to restore DC function.

Antisense proteinase 3 (PR3):a link between Staphylococcus aureus and PR3-ANCA associated vasculitis?
Projectleader: prof. dr. C.G.M. Kallenberg
University: UMC Groningen
E-mail: c.g.m.kallenberg@reuma.umcg.nl

The main goal of the project was to investigate whether anti-cPR3 antibodies are present in a Groningen cohort of patients with PR3-ANCA associated vasculitis. No increased anti-cPR3  reactivity in patients with PR3-ANCA associated vasculitis was found.  Also the possible role of Toll-like receptors (TLR) and  TLR-signaling in patients with ANCA-associated vasculitis was investigated. These studies are being finalized.

Defining the role of the intracellular suppressor-of-cytokine signalling (SOCS)-3 protein in cartilage pathology
Projectleader: dr. A.A.J. van de Loo
University: UMC st Radboud Nijmegen
E-mail: a.vandeloo@reuma.umcn.nl

This research showed that increased expression of SOCS3 in chondrocytes, whether or not by stimulation with IL-1 by adenoviral overexpression of SOCS3, can lead to insensitivity of these cells for IGF-1, one of the most important growth factors for chrondrocytes.

The cell type specific contribution of the different RcgR gene family members in the development of arthritis
Projectleader: Dr. J.S.Verbeek
University: LUMC Leiden
E-mail: j.s.verbeek@lumc.nl

The pilot experiments of this one-year project are the first analysis in its kind of the cell type specific role of the different FcgR in immune-complex driven disease models such as CIA using newly generated type specific FcgR KO mice on pure B6 background. The researchers could redefine the role of FcgRIIB and therefore solve a 10 year-on existing controverse.

The Nijmegen randomised controlled trial on the effectiveness of a multidisciplinary treatment programme in patients with OA of the Hands (NOAH)
Projectleader: dr. C.H.M. van den Ende
Institute: Sint Maartenskliniek Nijmegen
E-mail: e.vandenende@maartenskliniek.nl

In this study the researchers investigated the effectiveness of a multidimensional (a combination of education, exercise therapy, compensatory strategies and self management) treatment program. As compared with a monodisciplinairy intervention.150 patients were included in the study. The results are not yet reported or published and are expected at the end of 2011.

The contribution of antibody-facilitated immune effector systems in the pathogenis of RA
Projectleader: prof.dr. T.W.J. Huizinga
University: LUMC Leiden
E-mail: t.w.j.huizinga@lumc.nl

This project aimed to delineate the contribution of antibody-facilitated immune effector systems and the pathogenesis of RA through the genetic analyses.

The researchers performed several genetic studies in complement and Fc-Receptors genes and identified several significant associations to the predisposition to rheumatoid arthritis. It enhanced the knowledge of a very relevant locus and formed the basis for which new applications have been written.

Clinical and molecular classification of very early rheumatoid arthritis
Projectleader: prof. dr. P.P. Tak
University: AMC Amsterdam
E-mail: p.p.tak@amc.nl

In this study the researchers looked at the events in the earliest phases of the disease to discover novel potential diagnostic and prognostic markers.

Some results. All but one autoantibody-positive individuals (n=55) showed very low scores for phenotypic markers, adhesion molecules, and vascularity, all in the same range as those in normal controls. Based on these results the researchers conclude that subclinical inflammation of the synovium does not coincide with the appearance of serum auto-antibodies during the pre-RA stage. Suggesting that a 'second hit' is involved.

So this study supports the rationale for exploring preventive strategies aimed at interfering with the humoral immune response before synovial inflammation develops.