Peripheral Blood Stem Cells of Patients with Systemic Lupus Erythematosus Show Altered Differentiation into Macrophages

ABSTRACT

Patients with systemic lupus erythematosus (SLE) often display clearance deficiencies for various targets like apoptotic cells. Most of the in vitro phagocytosis assays have been performed with leukocyte preparations from patients with SLE and may, therefore, be influenced by immunosuppressive drugs. We isolated circulating hematopoietic stem cells from patients with SLE to generate adherent cells in vitro and to evaluate their phenotype in the absence of any therapeutic influence. CD34+/CD45+ stem cells were sorted with a cell sorter out from peripheral blood and cultured in methylcellulose-based medium. Differentiation into adherent cells was induced by culture of colony forming cells in medium containing granulocyte-macrophage colony-stimulating factor (GM-CSF). The cell cycle and cell death of CD34+/CD45+ stem cell-derived cells were not altered in patients with SLE. However, the differentiated cells showed disturbed adhesion and altered morphology in patients with SLE. Adherent cells derived from patients with SLE failed to express CD11, CD14, CD45, and CD16. Furthermore, the phagocytosis of IgG coated beads by stem cell-derived adherent cells was impaired in the case of SLE. We suggest that the impaired clearance of apoptotic cells seen in patients with SLE may involve intrinsic defects in the differentiation of myeloid progenitors.

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