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


CONCLUSIONS
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.
Thompson
S D
SD
William S. Rowe Division of Rheumatology, Children's Hospital Medical Center, Department of Pediatrics, University of Cincinnati, College of Medicine, OH, USA.
Grom
A A
AA
Bailey
S
S
Luyrink
L
L
Giannini
E H
EH
Murray
K
K
Passo
M H
MH
Lovell
D J
DJ
Choi
E
E
Glass
D N
DN
D000595:Amino Acid Sequence; D001171:Arthritis, Juvenile / Q000276:immunology*; D002999:Clone Cells / Q000276:immunology; D018076:DNA, Complementary / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D059810:HLA-DR Serological Subtypes; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D013582:Synovial Fluid / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018076:DNA, Complementary; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C041559:HLA-DR8 antigen; D011948:Receptors, Antigen, T-Cell