Increased apoptosis of bone marrow CD34(+) cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus.
The changes in bone marrow (BM) stem cell reserve and function and stromal cell function in patients with active systemic lupus erythematosus (SLE) were investigated. The study was carried out on seven SLE patients and 28 healthy controls using flow cytometry and in vitro cell culture assays. We found that patients had low CD34(+) cells, compared with the control group, reflecting the decrease of both CD34(+)/CD38(-) and CD34(+)/CD38(+) cells. Patient CD34(+)/Fas(+) but not CD34(-)/Fas(+) cells were significantly increased. Apoptotic (7AAD(dim)) cells were higher among CD34(+)/Fas(+) than among CD34(+)/Fas(-) cells, and individual values of apoptotic CD34+ cells strongly correlated with the number of CD34(+)/Fas(+) cells. These findings are suggestive of a Fas-mediated apoptosis accounting for the low CD34(+) cells in SLE patients. Moreover, we found that patients had low numbers of granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E), compared with the control group, and that the generation of colony-forming cells in long-term BM cultures was significantly reduced. Patient BM stroma failed to support allogeneic progenitor cell growth. In one patient, CD34(+) cells were increased, apoptotic CD34(+)/Fas(+) cells were normalized and defective stromal cell function was restored after autologous stem cell transplantation. We concluded that defective haemopoiesis in SLE patients is probably caused, at least in part, to the presence of autoreactive lymphocytes in BM.
Papadaki
H A
HA
Department of Haematology, University of Crete School of Medicine, Crete, Greece. epapadak@med.uoc.gr
Boumpas
D T
DT
Gibson
F M
FM
Jayne
D R
DR
Axford
J S
JS
Gordon-Smith
E C
EC
Marsh
J C
JC
Eliopoulos
G D
GD
D000328:Adult; D000704:Analysis of Variance; D018952:Antigens, CD34 / Q000032:analysis*; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D005434:Flow Cytometry; D006410:Hematopoiesis; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007150:Immunohistochemistry; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D013234:Stem Cells / Q000276:immunology*; D013997:Time Factors; D019014:fas Receptor / Q000032:analysis
D018952:Antigens, CD34; D019014:fas Receptor