Impaired clearance of dying cells in systemic lupus erythematosus

Abstract: Impaired clearance of apoptotic cell material has been implicated in the pathogenesis of systemic lupus erythematosus (SLE). Besides many other molecules, C1q and DNaseI contribute to an efficient clearance of dying cells. A frequently observed factor in SLE patients is the accumulation of unusually large amounts of apoptotic cells in various tissues. We showed that in a subgroup of patients with SLE, apoptotic cells accumulated in the germinal centers of the lymph nodes. The numbers of tingible body macrophages usually containing engulfed apoptotic nuclei were significantly reduced in these patients. Furthermore, we differentiated macrophages from CD34+ stem cells of SLE patients and NHD in vitro to analyze whether the observed clearance defects are intrinsic. Indeed, macrophages from SLE patients showed a reduced phagocytic capability. Very interestingly, those macrophages from different SLE patients, as well as granulocytes from these patients, showed in part different phagocytic defects, suggesting a heterogeneous clearance defect. We conclude that a failure of clearance in the early phase of apoptosis leads to a secondary necrotic status of the cells. Danger signals are released, modified autoantigens are accessible, and an autoimmune reaction gets started. [Copyright &y& Elsevier]