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Increased apoptosis of bone marrow CD34 + cells and impaired function of bone marrow stromal cells in patients with systemic lupus erythematosus
Author(s) -
Papadaki Helen A.,
Boumpas Dimitrios T.,
Gibson Frances M.,
Jayne David R.,
Axford John S.,
GordonSmith E. C.,
Marsh Judith C. W.,
Eliopoulos George D.
Publication year - 2001
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2001.03076.x
Subject(s) - cd34 , stromal cell , bone marrow , cd38 , haematopoiesis , progenitor cell , stem cell , immunology , apoptosis , biology , medicine , cancer research , microbiology and biotechnology , biochemistry
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.