Patterns of T lymphocyte clonal expansion in HLA-typed patients with juvenile rheumatoid arthritis

Abstract

Objective: The presence of clonally expanded T lymphocytes appears to be a characteristic feature of autoimmune diseases, including juvenile rheumatoid arthritis (JRA), although the relevance of such clones to immunopathogenesis is not clear. Identification of clones specific for a disease and/or particular MHC haplotypes should help differentiate those of pathogenic importance.

Methods: A reverse transcriptase polymerase chain reaction assay for T cell receptor (TCR) complementarity determining region 3 (CDR3) length heterogeneity and cDNA sequencing were used to identify clonal expansion in synovial fluid (SF) samples obtained from 36 patients with JRA.

Results: The majority of patients had multiple synovial T cell clones using different TCR V beta families. Fifty-eight percent of these clonally expanded T cell populations used one of six TCR V beta families (V beta 2, V beta 8, V beta 14, V beta 16, V beta 17, and V beta 20). Patients with polyarticular, as opposed to pauciarticular, JRA had higher numbers of clones in joints. TCR V beta 8, V beta 14, V beta 16, and V beta 17 families were most frequently found in these clones. Overall, the most frequently used V beta family was V beta 20, which was observed in 18 of 36 SF samples. Of 18 patients exhibiting TCR V beta 20 clonal expansion, 14 (78%) had pauciarticular onset JRA. The V beta 20 association was especially strong in patients who possessed HLA-DR8+ haplotypes (p = 0.01, Fisher's exact test). SF from the patients who had other types of JRA (and other MHC haplotypes) did not show this association.

Conclusion: The distinct clinical subtypes of JRA are characterized by different patterns of synovial T cell clonality. These findings imply that different molecular pathways underlie the development of arthritis in each subtype of JRA.