Apoptosis of CD34+ cells after incubation with sera of leukopenic patients with systemic lupus erythematosus.
Leukopenia and anaemia are observed in about a fifth of all patients with systemic lupus erythematosus (SLE) and may be due either to the destruction of blood cells or their decreased production. The former may be humoral or cell-mediated or result from apoptosis of peripheral blood cells. Several observations suggest the occurrence of the latter reduced in vitro proliferation of pluripotent bone marrow progenitors from the bone marrow aspirates of SLE patients,reduced counts of CD34+ cells in bone marrow aspirates in SLE patients, apoptosis of lymphopoietic progenitors and apoptosis of bone marrow cells. The aim of our study was to investigate whether humoral factors may induce suppression of haematopoiesis by increased apoptosis of CD34+ cells. For this purpose, we incubated allogeneic CD34+-enriched cells with sera of 18 leukopenic SLE patients. Apoptosis was induced by four of 18 sera. This effect was independent of complement-inhibition and FAS-blockade. Although reduced proliferation of autologous pluripotent bone marrow progenitors has been attributed to an IgG serum inhibitor, removal of IgG from these four proapoptotic sera had no effect on apoptosis of allogeneic CD34+ cells. The proapoptotic effect was associated with high titres of anti-dsDNA antibodies and low haemoglobin concentrations, but not with high titres of antinuclear antibodies, TNF-alpha and IFN-alpha of the sera tested.
Tiefenthaler
M
M
Department of Nephrology, University of Innsbruck, Innsbruck, Austria. martin.tiefenthaler@uibk.ac.at
Bacher
N
N
Linert
H
H
Mühlmann
O
O
Hofer
S
S
Sepp
N
N
Amberger
A
A
Geisen
F
F
Obermoser
G
G
Konwalinka
G
G
D018952:Antigens, CD34 / Q000276:immunology*; D017209:Apoptosis / Q000502:physiology*; D001854:Bone Marrow Cells / Q000276:immunology*; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000276:immunology / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D016898:Interferon-alpha / Q000032:analysis; D007970:Leukopenia / Q000097:blood*; D008180:Lupus Erythematosus, Systemic / Q000097:blood*; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018952:Antigens, CD34; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha