title: Serum with phospholipase A2 receptor autoantibodies interferes with podocyte adhesion to collagen.
abstract: BACKGROUND
  The majority of sera from patients with primary membranous nephropathy have autoantibodies against the M-type phospholipase A2 receptor (PLA2R) which is expressed on human podocytes. The rabbit variant of PLA2R attaches to collagen type IV via the fibronectin type II domain, which is also present in the human variant of PLA2R.
  
  
  METHODS
  To assess whether the human PLA2R variant is also involved in attachment to collagen type IV, we conducted a cell adhesion assay on a collagen-coated surface using PLA2R-transfected and mock-transfected human embryonic kidney (HEK) cells. To test the hypothesis that sera from patients containing anti-PLA2R antibodies interfere with the adhesion of podocytes to collagen, we performed cell adhesion assays on a collagen type IV-coated surface using positive and negative serum samples from patients and cultured human podocytes in vitro expressing PLA2R.
  
  
  RESULTS
  The HEK cell adhesion assay confirmed an enhanced attachment of PLA2R-transfected cells to collagen type IV. We confirmed diminished podocyte adhesion in the presence of serum with anti-PLA2R antibodies. The concentration of anti-PLA2R antibodies correlated with proteinuria and to the degree of diminished adhesion of podocytes.
  
  
  CONCLUSIONS
  We demonstrated that serum of patients containing autoantibodies directed to PLA2R interferes with the ability of podocytes to attach to collagen type IV in vitro, providing evidence of a serum soluble pathogenic factor interfering with podocyte adhesion in membranous nephropathy.
authors.affiliation: Division of Nephrology, Hannover Medical School, Hannover, Germany; Department of Nephrology, University Medical Centre Ljubljana, Ljubljana, Slovenia.
authors.forename: Andrej
authors.initials: A
authors.lastname: Škoberne
authors.forename: Astrid
authors.initials: A
authors.lastname: Behnert
authors.forename: Beina
authors.initials: B
authors.lastname: Teng
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
authors.forename: Lena
authors.initials: L
authors.lastname: Schiffer
authors.forename: Jernej
authors.initials: J
authors.lastname: Pajek
authors.forename: Jelka
authors.initials: J
authors.lastname: Lindič
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Mario
authors.initials: M
authors.lastname: Schiffer
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000494:pharmacology*; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000502:physiology*; D024141:Collagen Type IV / Q000378:metabolism / Q000502:physiology*; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000503:physiopathology; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000502:physiology*; D054507:Receptors, Phospholipase A2 / Q000276:immunology* / Q000378:metabolism; D044967:Serum / Q000502:physiology*; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D024141:Collagen Type IV; D054507:Receptors, Phospholipase A2
keywords: PLA2R antibodies; cell adhesion; collagen IV; podocyte; primary membranous nephropathy