TY - JOUR
T1 - Oligoclonal T cell proliferation in patients with rheumatoid arthritis and their unaffected siblings
AU - Waase, Inge
AU - Kayser, Corinna
AU - Carlson, Paula J.
AU - Goronzy, Jörg J.
AU - Weyand, Corelia M.
PY - 1996/6
Y1 - 1996/6
N2 - Objective. To analyze whether patients with rheumatoid arthritis (RA) have an intrinsic defect in T cell proliferation and survival, possibly contributing to the infiltration of the synovial membrane with CD4+ T cells. Methods. Fifteen patients with seropositive RA, 11 patients with psoriatic arthritis, 20 normal controls, and 9 affected and 13 unaffected siblings from 7 multiplex families with RA were analyzed for clonal proliferation. To investigate this clonal T cell proliferation, CD4+ T cells were purified from peripheral blood and synovial fluid by magnetic bead separation, T cell receptor (TCR) β-chain sequences were amplified by reverse transcriptase- polymerase chain reaction, using TCR BV and BJ gene segment-specific primer sets. Clonally expanded T cell specificities were identified by size fractionation and sequencing of the amplified product. Results. All RA patients carried clonally expanded CD4+ T cells in the peripheral blood compartment. Such expanded CD4+ T cell clonotypes were only infrequently observed both in normal individuals (P < 0.0001) and in patients with psoriatic arthritis (P = 0.004). Lymphoproliferation of selected CD4+ T cells was shared by affected and unaffected siblings from RA multiplex families (P = 0.005 and P = 0.0003, respectively, compared with normal controls). Expanded clonotypes persisted for several years and contributed to the T cell infiltrate in the joint. Clonal T cell proliferation involved a diverse spectrum of TCR molecules. Conclusion. RA patients have an abnormality in the homeostasis of CD4+ T cells, characterized by the emergence of clonally proliferating populations. The presence of clonal outgrowth of selected CD4+ T cell specificities in unaffected siblings of RA patients suggests that oligoclonality of CD4+ T cells is inherited and is a risk factor for, rather than a result of, synovial inflammation.
AB - Objective. To analyze whether patients with rheumatoid arthritis (RA) have an intrinsic defect in T cell proliferation and survival, possibly contributing to the infiltration of the synovial membrane with CD4+ T cells. Methods. Fifteen patients with seropositive RA, 11 patients with psoriatic arthritis, 20 normal controls, and 9 affected and 13 unaffected siblings from 7 multiplex families with RA were analyzed for clonal proliferation. To investigate this clonal T cell proliferation, CD4+ T cells were purified from peripheral blood and synovial fluid by magnetic bead separation, T cell receptor (TCR) β-chain sequences were amplified by reverse transcriptase- polymerase chain reaction, using TCR BV and BJ gene segment-specific primer sets. Clonally expanded T cell specificities were identified by size fractionation and sequencing of the amplified product. Results. All RA patients carried clonally expanded CD4+ T cells in the peripheral blood compartment. Such expanded CD4+ T cell clonotypes were only infrequently observed both in normal individuals (P < 0.0001) and in patients with psoriatic arthritis (P = 0.004). Lymphoproliferation of selected CD4+ T cells was shared by affected and unaffected siblings from RA multiplex families (P = 0.005 and P = 0.0003, respectively, compared with normal controls). Expanded clonotypes persisted for several years and contributed to the T cell infiltrate in the joint. Clonal T cell proliferation involved a diverse spectrum of TCR molecules. Conclusion. RA patients have an abnormality in the homeostasis of CD4+ T cells, characterized by the emergence of clonally proliferating populations. The presence of clonal outgrowth of selected CD4+ T cell specificities in unaffected siblings of RA patients suggests that oligoclonality of CD4+ T cells is inherited and is a risk factor for, rather than a result of, synovial inflammation.
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U2 - 10.1002/art.1780390606
DO - 10.1002/art.1780390606
M3 - Article
C2 - 8651983
AN - SCOPUS:0029939649
SN - 0004-3591
VL - 39
SP - 904
EP - 913
JO - Arthritis and rheumatism
JF - Arthritis and rheumatism
IS - 6
ER -