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IgG autoantibodies bound to surfaces of necrotic cells and complement C4 comprise the phagocytosis promoting activity for necrotic cells of SLE sera
  1. Gerhard E Grossmayer (gegro{at}gmx.net)
  1. Institute for Clinical Immunology, Department for Internal Medicine 3, University of Erlangen, Germany
    1. Luis E Munoz (luis.munoz{at}uk-erlangen.de)
    1. Institute for Clinical Immunology, Department for Internal Medicine 3, University of Erlangen, Germany
      1. Christian K Weber (cweber{at}molmed.uni-erlangen.de)
      1. IZKF Research Group 2, University Hospital Erlangen, Germany
        1. Sandra Franz (sandra.franz{at}uk-erlangen.de)
        1. Institute for Clinical Immunology, Department for Internal Medicine 3, University of Erlangen, Germany
          1. Reinhard E Voll (rvoll{at}molmed.uni-erlangen.de)
          1. IZKF Research Group 2, University Hospital Erlangen, Germany
            1. Peter M Kern (peter.kern{at}franz-von-pruemmer-klinik.de)
            1. Franz von Prümmer Klinik, Germany
              1. Joachim R Kalden (jkalden{at}molmed.uni-erlangen.de)
              1. Institute for Clinical Immunology, Department for Internal Medicine 3, University of Erlangen, Germany
                1. Georg Schett (georg.schett{at}uk-erlangen.de)
                1. Institute for Clinical Immunology, Department for Internal Medicine 3, University of Erlangen, Germany
                  1. Martin Herrmann (martin.herrmann{at}uk-erlangen.de)
                  1. Institute for Clinical Immunology, Department for Internal Medicine 3, University of Erlangen, Germany
                    1. Udo S Gaipl (udo.gaipl{at}uk-erlangen.de)
                    1. Institute for Clinical Immunology, Department for Internal Medicine 3, University of Erlangen, Germany

                      Abstract

                      Objective: Accumulation of dying and dead cells is discussed to be involved in the etiopathogenesis of systemic lupus erythematosus (SLE). Clearance has been described mainly for apoptotic cells; however, the knowledge of serum factors participating in the phagocytosis of necrotic cells is scarce.

                      Patients and Methods: Sera from 18 SLE patients and 10 normal healthy donors (NHD) and macrophages from 3 NHD were included. Autoantibodies and complement were measured by ELISA and phagocytosis by flow cytometry. Binding of serum IgG to necrotic cells was assessed by flow cytometry and confocal microscopy.

                      Results: Sera from patients with SLE and NHD generally promoted the phagocytosis of necrotic cells by macrophages isolated from NHD. Five independent experiments with macrophages from three different NHD led to similar results. The healthy controls’ sera displayed a homogeneous activity, whereas sera of SLE patients showed a dichotomic behaviour. Only sera containing autoantibodies binding to the surfaces of necrotic cells and sufficient complement showed increased phagocytosis promoting activities. In SLE sera C4 turned out to be the critical complement component in this process. Sera de-complemented by heat treatment strongly reduced phagocytosis of necrotic cells.

                      Conclusions: Serum components influence the uptake of necrotic cells by phagocytosis competent macrophages from NHD. Complement is required for this process and autoantibodies binding to the surfaces of necrotic cells additionally promote their phagocytosis.

                      • SLE
                      • autoantibodies
                      • complement
                      • necrotic cells
                      • phagocytosis

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