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Dynamic T cell receptor clonotype changes in synovial tissue of patients with early rheumatoid arthritis : effects of treatment with cyclosporin A (Neoral®)

(2002) JOURNAL OF RHEUMATOLOGY. 29(3). p.416-426
Author
Organization
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.
Keywords
DISEASE, MICROEMULSION, APOPTOSIS, REPERTOIRE, GENE USAGE, QUANTITATIVE-ANALYSIS, MICROSCOPIC MEASUREMENT, cyclosporin A, T cell receptor repertoire, autoimmunity, rheumatoid arthritis, synovium, PERSISTENCE, VACCINATION, MEMBRANE

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Chicago
VanderBorght, Ann, Filip De Keyser, Piet Geusens, Marc De Backer, Michel Malaise, Dominique Baeten, Filip Van den Bosch, Eric Veys, Jef Raus, and Piet Stinissen. 2002. “Dynamic T Cell Receptor Clonotype Changes in Synovial Tissue of Patients with Early Rheumatoid Arthritis : Effects of Treatment with Cyclosporin A (Neoral®).” Journal of Rheumatology 29 (3): 416–426.
APA
VanderBorght, A., De Keyser, F., Geusens, P., De Backer, M., Malaise, M., Baeten, D., Van den Bosch, F., et al. (2002). Dynamic T cell receptor clonotype changes in synovial tissue of patients with early rheumatoid arthritis : effects of treatment with cyclosporin A (Neoral®). JOURNAL OF RHEUMATOLOGY, 29(3), 416–426.
Vancouver
1.
VanderBorght A, De Keyser F, Geusens P, De Backer M, Malaise M, Baeten D, et al. Dynamic T cell receptor clonotype changes in synovial tissue of patients with early rheumatoid arthritis : effects of treatment with cyclosporin A (Neoral®). JOURNAL OF RHEUMATOLOGY. 2002;29(3):416–26.
MLA
VanderBorght, Ann, Filip De Keyser, Piet Geusens, et al. “Dynamic T Cell Receptor Clonotype Changes in Synovial Tissue of Patients with Early Rheumatoid Arthritis : Effects of Treatment with Cyclosporin A (Neoral®).” JOURNAL OF RHEUMATOLOGY 29.3 (2002): 416–426. Print.
@article{165174,
  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.},
  author       = {VanderBorght, Ann and De Keyser, Filip and Geusens, Piet and De Backer, Marc and Malaise, Michel and Baeten, Dominique and Van den Bosch, Filip and Veys, Eric and Raus, Jef and Stinissen, Piet},
  issn         = {0315-162X},
  journal      = {JOURNAL OF RHEUMATOLOGY},
  keywords     = {DISEASE,MICROEMULSION,APOPTOSIS,REPERTOIRE,GENE USAGE,QUANTITATIVE-ANALYSIS,MICROSCOPIC MEASUREMENT,cyclosporin A,T cell receptor repertoire,autoimmunity,rheumatoid arthritis,synovium,PERSISTENCE,VACCINATION,MEMBRANE},
  language     = {eng},
  number       = {3},
  pages        = {416--426},
  title        = {Dynamic T cell receptor clonotype changes in synovial tissue of patients with early rheumatoid arthritis : effects of treatment with cyclosporin A (Neoral®)},
  url          = {http://www.jrheum.org/content/29/3/416},
  volume       = {29},
  year         = {2002},
}

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