Dominant T-cell-receptor beta chain variable region V beta 14+ clones in juvenile rheumatoid arthritis.
The characteristic histopathology and major histocompatibility complex associations in juvenile rheumatoid arthritis suggest an oligoclonal antigen-specific T-cell population may be critical to pathogenesis. To test this, we analyzed the T-cell repertoire of a polyarticular HLA-DR4+ juvenile rheumatoid arthritis patient with an aggressive form of disease that required arthrocentesis of the knee joints and early replacement of both hip joints. A comparison of T-cell-receptor beta chain variable region (V beta) gene expression in peripheral blood and synovial fluid performed by semiquantitation of cDNA samples amplified by the PCR revealed overexpression of the T-cell-receptor V beta 14 gene family. To determine the nature of V beta 14 overexpression, we sequenced randomly cloned amplification products derived from two synovial fluid, two synovial tissue, and three peripheral blood samples by using a V beta 14/beta chain constant region primer pair. Sequence data showed that the T-cell response in the synovia was oligoclonal. Of four clones found, one was present in all joints examined and persisted over time. This clone accounted for 67% and 74% of all V beta 14+ clones sequenced in two synovial fluid samples and 75% and 40% in two synovial tissue samples. This clone was also found at a lesser frequency in peripheral blood samples. Further studies provided evidence for the presence of oligoclonally expanded populations of T cells utilizing the V beta 14 T-cell receptor in 6 of 27 patients examined. In contrast to the remaining patients studied, 3 with a late onset polyarticular course who exhibited especially marked clonality were characterized by features typical of adult rheumatoid arthritis (IgM rheumatoid factor-positive and HLA-DR4+). These data suggest a role for V beta 14+ T cells in a group of juvenile rheumatoid arthritis patients.
Grom
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AA
Division of Rheumatology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039.
Thompson
S D
SD
Luyrink
L
L
Passo
M
M
Choi
E
E
Glass
D N
DN
D000595:Amino Acid Sequence; D001171:Arthritis, Juvenile / Q000235:genetics*; D001483:Base Sequence; D002999:Clone Cells; D015870:Gene Expression; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005796:Genes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000166:cytology*; D013997:Time Factors
D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta