title: Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis.
abstract: OBJECTIVE
  Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN.
  
  
  METHODS
  Human podocyte and glomerular proteins were separated by SDS-PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC-MS/MS.
  
  
  RESULTS
  LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36 and 50 kDa in glomerular extracts. Those bands were analyzed by LC-MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2.
  
  
  CONCLUSIONS
  Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers.
authors.affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.|Robley Rex Veterans Affairs Medical Center, Louisville, KY, USA.
authors.forename: Dawn J
authors.initials: DJ
authors.lastname: Caster
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Korte
authors.affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Merchant
authors.affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.|Robley Rex Veterans Affairs Medical Center, Louisville, KY, USA.
authors.forename: Jon B
authors.initials: JB
authors.lastname: Klein
authors.affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Wilkey
authors.affiliation: Department of Medicine, the Ohio State University, Columbus, OH, USA.
authors.forename: Brad H
authors.initials: BH
authors.lastname: Rovin
authors.affiliation: Department of Medicine, the Ohio State University, Columbus, OH, USA.
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Birmingham
authors.affiliation: Center for Autoimmune Genomics and Etiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati, Cincinnati, OH, USA.|US Department of Veterans Affairs Medical Center, Cincinnati, OH, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Harley
authors.affiliation: Center for Autoimmune Genomics and Etiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Beth L
authors.initials: BL
authors.lastname: Cobb
authors.affiliation: Center for Autoimmune Genomics and Etiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center and the University of Cincinnati, Cincinnati, OH, USA.
authors.forename: Bahram
authors.initials: B
authors.lastname: Namjou
authors.affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.|Robley Rex Veterans Affairs Medical Center, Louisville, KY, USA.
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: McLeish
authors.affiliation: Department of Medicine, University of Louisville School of Medicine, Louisville, KY, USA.|Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Powell
mesh_terms: D017306:Annexin A2 / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D008181:Lupus Nephritis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: D017306:Annexin A2; D001323:Autoantibodies
keywords: Autoantibodies; Glomerulonephritis; Lupus nephritis; Systemic lupus erythematosus; Target antigens
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