title: Combination of autoantibodies against different histone proteins influences complement-dependent phagocytosis of necrotic cell material by polymorphonuclear leukocytes in systemic lupus erythematosus.
abstract: OBJECTIVE
  Polymorphonuclear leukocytes (PMN) with autoantibody-coated engulfed necrotic cell material (NC) are frequently seen in systemic lupus erythematosus (SLE). We evaluated the roles of complement, different antihistone antibodies (anti-H ab), and oxidative burst in the phagocytosis of NC by PMN, as well as association to disease activity and clinical phenotype in SLE.
  
  
  METHODS
  ELISA and immunoblot were used to measure antibodies to different histone proteins in sera from patients with SLE and complement-deficient individuals. Phagocytosis of NC by PMN and oxidative burst activity was assessed by flow cytometry.
  
  
  RESULTS
  A clearly increased phagocytosis of NC was seen in patients with active SLE, which was associated with high levels of anti-H ab concentrations and oxidative burst activity. The complement system contributed to efficient phagocytosis of NC by PMN through activation of the classical pathway, and the phagocytosis was mediated by FcγRIIA, FcγRIIIB, and CR1 in combination. A pattern of high phagocytosis, consumption of classical pathway components, and a broad anti-H ab repertoire was seen particularly in patients with nephritis and serositis. The combination of antibodies to several different histone proteins, often with anti-DNA antibodies, promoted an efficient uptake of NC, whereas antibodies against only histone H1 or a few histones seemed to be of less importance.
  
  
  CONCLUSIONS
  The distributions of specificities among anti-H ab are of great importance in the complement-dependent phagocytosis of debris from NC in SLE. Measurement of anti-H ab could be useful in monitoring of this disease and contribute to improved understanding of the autoimmune process.
authors: Department of Laboratory Medicine, Lund University, Lund, Sweden. Birgitta.Gullstrand@med.lu.se
authors: Birgitta
authors: B
authors: Gullstrand
authors: Malin H
authors: MH
authors: Lefort
authors: Helena
authors: H
authors: Tydén
authors: Andreas
authors: A
authors: Jönsen
authors: Christian
authors: C
authors: Lood
authors: Asa
authors: A
authors: Johansson
authors: Søren
authors: S
authors: Jacobsen
authors: Lennart
authors: L
authors: Truedsson
authors: Anders A
authors: AA
authors: Bengtsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000276:immunology* / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006657:Histones / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009336:Necrosis / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism; D010587:Phagocytosis / Q000276:immunology*; D011446:Prospective Studies
chemical_list: D001323:Autoantibodies; D006657:Histones; D003165:Complement System Proteins