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1.1 Disease specific divergence of T cell receptor (TCR) oligoclonality in juvenile idiopathic arthritis (JIA)
We used a highly sensitive molecular heteroduplex technique to track specific clonality of TCR expressed by synovial T cells from children with JIA.1 We observed non-overlapping oligoclonality compared with peripheral T cells, with large clonal expansions which may be identical in different joints and persist over several years. Although synovial T cells have a highly activated phenotype (mostly CD45RO+ and HLA-DR+), we showed that the oligoclonal patterns differ from CD45RO+ cells in peripheral T cells. We also showed that dominant synovial T cell clones from children with oligoarticular JIA are in the CD4+ population, whereas in children with HLA-B27+ (enthesitis-related) arthritis large T cell clones dominate in the CD8+ population. Sequencing and reanalysing the whole TCR repertoire with N-region-specific sequences confirmed that these clones are at a very low frequency (less than 1 in 50 000 cells) in peripheral blood. This unexpected divergence is now being investigated at the level of antigen-specific T cells using major histocompatibility complex/peptide tetramers.
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1.2 Serum and synovial fluid concentrations of vascular endothelial growth factor (VEGF) in juvenile idiopathic arthritis (JIA)
Background—VEGF is a potent endothelial cell-specific mitogen as well as an angiogenic and vascular permeabilising cytokine. Recently, several studies indicated its involvement in the pathogenesis of synovitis in rheumatoid arthritis (RA) as an important agent for neoangiogenesis and changes in vascular permeability of synovial RA pannus.
Objective—To examine the role of VEGF in the pathogenesis of synovitis in JIA.
Patients and methods—Serum samples from 30 patients affected with active JIA (14 poly, 26 oligo) were evaluated with ELISA for VEGF (Amersham, UK) and p75 tumour necrosis factor soluble receptor (sTNFR) (Medgenix, Belgium) concentration. Corresponding VEGF and p75 sTNFR synovial fluid (SF) concentrations were evaluated in 20 patients. Data were compared with those from 10 patients with oligo-JIA in the remission phase and 10 controls.
Results—In patients with active poly-JIA and oligo-JIA, …
Footnotes
Supported by the Wellcome Trust, UK.
Footnotes
This study was supported by the Scientific and Technical Research Council of Turkey.
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This work was funded by the ARC.
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Supported by the DFG and the NIH, Grant AI 31229.