TCRbeta  spectratyping in RA: evidence of clonal expansions in peripheral blood lymphocytes

doi:10.1136/ard.57.5.319

Annals of the Rheumatic Diseases 1998;57:319-322; doi:10.1136/ard.57.5.319

Ann Rheum Dis 1998;57:319-322 ( May )

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TCR $beta$ spectratyping in RA: evidence of clonal expansions in peripheral blood lymphocytes F C Hall,^a K Thomson,^a J Procter,^b A J McMichael,^c B P Wordsworth^a

^a Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford, ^b Oxford Transplant Centre Tissue Typing Laboratory, Churchill Hospital, Oxford, ^c Institute of Molecular Medicine, John Radcliffe Hospital, Oxford

Correspondence to: Dr F C Hall, Department of Microbiology and Immunology, Fairchild Building D345, Stanford University, CA 94605-5124, USA.

Accepted for publication 4 March 1998

OBJECTIVE $---$ To compare the TCR $beta$ repertoire of peripheral blood CD8 enriched (CD8+) and depleted (CD8 $-$ ) T cells in rheumatoid arthritis(RA) patients and controls using CDR3 length analysis(spectratyping).
METHODS $---$ CD8+ and CD8 $-$ T cells were separated from 14 RA patients and 12 controls, using magnetic beads coated with anti-CD8 monoclonalantibodies. cDNA was prepared as the template for amplificationwith 22 V $beta$ -C $beta$ primer pairs. The products were resolved by electrophoresisin an ABI373 sequencer using GENESCAN software. Expansions wereidentified as dominant CDR3 lengths, where the area underlyingthe corresponding peak exceeded the sum of the areas of the twoadjacent peaks. This method was validated by sequencing 10 samplesdisplaying dominant peaks. The expansion frequencies in RA patientsand controls were compared using the $chi$ ² teststatistic.
RESULTS $---$ Dominant peaks were evident in several V $beta$ families. They were more frequent in RA patients in both the CD8+ subset (RA normalisedfrequency 10.6; control normalised frequency 8.0; p=0.03) andthe CD8 $-$ subset (RA normalised frequency 2.9; control normalisedfrequency 1.5; p=0.02). Sequencing of 10 samples exhibiting dominantpeaks revealed an unequivocal clonal expansion in nine (90%).
CONCLUSIONS $---$ RA patients exhibited a significantly increased frequency of T cell expansions both in the CD8+ and CD8 $-$ subsets. This phenomenonmay reflect the proliferation of autoreactive cells, a non-specificexpansion of memory T cells in response to pro-inflammatory cytokinesor a defect of T cell regulation that predates the onset of RAand may itself predipose todisease.

Keywords: rheumatoid arthritis; T cell; clonal expansion

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