Clearance of Apoptotic Cells in Human SLEGaipl U. · Kuhn A. · Sheriff A. · Munoz L. · Franz S. · Voll R. · Kalden J. · Herrmann M.
aInstitute for Clinical Immunology, Department of Medicine III, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, bDepartment of Dermatology, University of Düsseldorf, Düsseldorf, and cIZKF Research Group 2, Nikolaus-Fiebiger Center of Molecular Medicine, Erlangen, Germany
Systemic lupus erythematosus (SLE) is characterized by a diverse array of autoantibodies, particularly against nuclear antigens, thought to derive from apoptotic and necrotic cells. Impaired clearance functions for dying cells may explain accumulation of apoptotic cells in SLE tissues, and secondary necrosis of these cells may contribute to the chronic inflammation in this disease. The exposure of phosphatidylserine (PS) and altered carbohydrates on dying cells are important recognition signals for macrophages. Furthermore, serum factors such as complement, DNase I, pentraxins (e.g. C-reactive protein) and IgM contribute to efficient opsonization and uptake of apoptotic and necrotic cells. Defects in these factors may impact the development of SLE in humans and mice in a variety of ways. We observed impaired clearance of apoptotic cells in lymph nodes and skin biopsies of humans with lupus, as well as intrinsic defects of macrophages differentiated in vitro from SLE patients’ CD34+ stem cells, demonstrating that apoptotic cells are not properly cleared in a subgroup of patients with SLE. This altered mechanism for the clearance of dying cells may represent a central pathogenic process in the development and acceleration of this autoimmune disease.