Evidence of clonotypic pattern of T-cell repertoire in synovial fluid of children with juvenile rheumatoid arthritis at the onset of the disease

Scand J Immunol. 2002 Nov;56(5):512-7. doi: 10.1046/j.1365-3083.2002.01153.x.

Abstract

Rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) are characterized by chronic inflammation, synovial cell proliferation and progressive joint damage. It has been speculated that T cells play an important role in the pathogenesis of RA and JRA in the early stage of the disease. Previous studies have demonstrated discrepant results regarding the significance of T-cell clonality in RA or JRA lesions. It can be postulated that the heterogeneity of these data may be linked to the stage of the disease, as the relative importance of selective immunological events is different during the time from onset to established disease. To avoid this problem, we conducted the present study in nine children affected by JRA at the onset of the disease and before treatment. We analysed the T-cell receptor beta chain variable (TCRBV) of CD4+ and CD8+ lymphocytes in peripheral blood (PBL) and synovial fluid (SFL), by a panel of monoclonal antibodies (MoAbs). Furthermore, to assess the clonotypic pattern of T-cell repertoire, the CDR3 length distribution was evaluated by spectratyping analysis. Our results showed no significant expansion of distinct TCRBV subset in either synovial or peripheral compartments. Conversely, when we studied the CDR3 length distribution, an oligoclonal pattern was found in the SFL of six patients, suggesting the presence of a clonotypic restriction of T cells in SFL, which is not detectable in PBL. These findings are consistent with an antigen driven T-cell expansion sequestered at the inflammatory site.

MeSH terms

  • Antibodies, Monoclonal
  • Arthritis, Juvenile / etiology
  • Arthritis, Juvenile / genetics
  • Arthritis, Juvenile / immunology*
  • Arthritis, Juvenile / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / pathology
  • Child
  • Child, Preschool
  • Complementarity Determining Regions / genetics
  • Female
  • Humans
  • Male
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Complementarity Determining Regions
  • Receptors, Antigen, T-Cell, alpha-beta