The role of a defective clearance in the pathogenesis of systemic lupus erythematosus

Impaired clearance of apoptotic cell material has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). We analyzed the phagocytotic potency of macrophages differentiated from CD34-positive stem cells derived from the peripheral blood from SLE patients and normal healthy donors (NHD), respectively. Furthermore, we examined the uptake of beads and dying cells by granulocytes of SLE patients and NHD.

We found that, in a subgroup of SLE patients, the proliferation and differentiation patterns of the stem cells were different in comparison with NHD. Furthermore, in SLE patients a significantly reduced number of macrophages differentiated out of the stem cells. Additionally, the uptake capacity of some macrophages of SLE patients was reduced in comparison with NHD. Regarding the phagocytosis of albumin beads, polyglobuline beads, apoptotic and necrotic cells as well as degraded chromatin, we found that macrophages and/or granulocytes of some SLE patients showed a strongly reduced uptake of the prey.

The defective clearance of dying cells in a subgroup of SLE patients seems to be an intrinsic defect because fewer macrophages differentiated out of stem cells, and some of the generated phagocytes also showed reduced uptake efficiency. Furthermore, the impaired clearance capacities of granulocytes from some SLE patients could play an important role in the development of autoimmunity.