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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/2596

Title: Dynamic T cell receptor clonotype changes in synovial tissue of patients with early rheumatoid arthritis: Effects of treatment with cyclosporin A (Neoral (R))
Authors: Vander Borght, Ann
De Keyser, F.
De Backer, M.
Malaise, M.
Baeten, D.
Van den Bosch, F.
Veys, E.M.
Geusens, Piet
Raus, Jef
Stinissen, Piet
Issue Date: 2002
Publisher: J RHEUMATOL PUBL CO
Citation: JOURNAL OF RHEUMATOLOGY, 29(3). p. 416-426
Abstract: Objective. To study T cell receptor (TCR) repertoire changes in synovial membrane over a 16 week period in patients with early rheumatoid arthritis (RA); and to study the influence of cyclosporin A (CSA) on TCR repertoire in a subgroup of these patients. Methods. Synovial tissue biopsies and paired blood samples were obtained from 12 patients with early RA at 2 time points. Seven patients were treated with CSA (Neoral-Sandimmun(R), 3 mg/kg/day) and 5 patients with placebo for 16 weeks. TCR V gene repertoires were analyzed by semiquantitative PCR-ELISA. CDR3 spectratyping and sequence analysis was used to compare TCR clonotype distributions. Results. TCR-specific mRNA was detected in all synovial tissue biopsies at the first sampling, but in only 8/12 biopsies 16 weeks later (4/7 CSA group, 4/5 placebo group). Overrepresented TCR BV genes were found in biopsies of 10/12 patients at the First time point, and in 7/12 patients after 16 weeks (3/7 CSA, 4/5 placebo). CDR3 sequence analysis revealed dynamic repertoire changes with only a few Persisting clonotypes in the synovial tissue of placebo controls. Persisting T cell clonotypes were more frequently found in the synovial tissue of CSA treated patients compared to the placebo group. Conclusion. These data suggest a dynamic process of T cell recruitment in the joints of RA patients. This process, possibly due to activation and subsequent infiltration of new T cell clones, apparently is influenced by CSA treatment. Synovial tissue T cells were no longer detected after 16 weeks' CSA treatment in 3 patients. In the other CSA treated patients, new T cell clones infiltrated, while other clones were persistently represented in the joints. These data may have important consequences for the design of T cell targeted therapies for PA.
Notes: Limburgs Univ Ctr, Onderzoeksinst DWI, B-3590 Diepenbeek, Belgium. State Univ Ghent, Dept Rheumatol, Brussels, Belgium. Novartis Pharma, Brussels, Belgium. Univ Liege, Dept Rheumatol, Liege, Belgium.Stinissen, P, Limburgs Univ Ctr, Onderzoeksinst DWI, Univ Campus, B-3590 Diepenbeek, Belgium.
URI: http://hdl.handle.net/1942/2596
Link to publication: http://jrheum.com/abstracts/abstracts02/416.html
ISI #: 000174214100003
ISSN: 0315-162X
Category: A1
Type: Journal Contribution
Validation: ecoom, 2003
Appears in Collections: Research publications

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