Clonal characteristics of T cell infiltrates in skin and synovium of patients with psoriatic arthritis.
Psoriasis is a chronic inflammatory skin disease that is often complicated by an inflammatory arthritis. Considerable evidence implicates cellular immune responses in psoriatic skin lesions, but the pathogenesis of the associated arthritis has not been elucidated. We analyzed T cell antigen receptor beta chain variable (TCRbetaV) gene repertoires among peripheral blood lymphocytes, skin and synovium of nine patients with psoriatic arthritis. RNase protection assays were used to quantitate the expression levels of 25 TCRbetaV genes, and CDR3 region sequencing was used to further characterize selected expansions. All patients exhibited significant TCRbetaV biases in the peripheral blood and moreover, all had expansions common to both skin and synovium. CDR3 sequencing demonstrated these expansions frequently consisted of oligo- or monoclonal populations. Although no ubiquitous CDR3 nucleotide sequences were identified, two patients shared identical sequences and several highly homologous amino acid motifs were present in skin and synovium among and between individual patients. Findings of common TCRbetaV expansions in diverse inflammatory sites, among multiple afflicted individuals, suggest that these T cell proliferations are driven by engagements with a limited set of conventional antigens. These findings demonstrate an important role for cognate T cell responses in the pathogenesis of psoriatic arthritis, and further suggest the inciting antigen(s) is identical or homologous between afflicted skin and synovium.
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892-1828, USA.
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I
Tassiulas
S R
SR
Duncan
M
M
Centola
A N
AN
Theofilopoulos
D T
DT
Boumpas
D000328:Adult; D000595:Amino Acid Sequence; D015535:Arthritis, Psoriatic / Q000097:blood / Q000276:immunology* / Q000473:pathology; D001483:Base Sequence; D002999:Clone Cells; D006801:Humans; D007963:Leukocytes, Mononuclear; D008875:Middle Aged; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D012867:Skin / Q000276:immunology* / Q000473:pathology; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta