title: No complement receptor 1 stumps on podocytes in human glomerulopathies.
abstract: BACKGROUND
  Type one complement receptor (CR1) is the only physiological inhibitor of complement on podocytes. CR1 is lost in different glomerulopathies, in particular in lupus nephritis, in which it has been suggested that CR1 is removed by proteolysis from the cell membrane.
  
  
  METHODS
  To define whether proteolytic cleavage of CR1 on podocytes is a general phenomenon, we analyzed the expression of CR1 in different glomerulopathies using a monoclonal antibody against epitopes present on the extracellular portion of the molecule and a polyclonal antibody directed at the intracellular tail of CR1. The two antibodies were applied on sequential serial histologic sections of renal biopsy.
  
  
  RESULTS
  In normal glomeruli, the two antibodies provided similar results, that is, strong staining of podocytes, and both were shown to recognize specifically CR1. Decreased expression of the extracellular portion of CR1 was observed in lupus nephritis (8/8), focal and segmental glomerulosclerosis (FSGS; 7/7), IgA nephritis (6/6), membranous glomerulonephritis (3/3), and minimal change disease (3/3). In each case, the decreased expression was accompanied by a simultaneous decrease of the expression of the intracellular tail of CR1 (Spearman's correlation coefficient rs = 0.951, P < 0.001). This observation was confirmed by analyzing focal glomerular lesions on sequential serial sections.
  
  
  CONCLUSIONS
  These data indicate that there are no CR1 stumps on podocytes, even in lupus nephritis, and suggest that the CR1 loss on podocytes is not due to consumption but to decreased synthesis. A loss of CR1 synthesis might render podocytes highly sensitive to complement attack.
authors.affiliation: Departments of Pathology and Research, Basel Medical School, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Moll
authors.forename: S
authors.initials: S
authors.lastname: Miot
authors.forename: S
authors.initials: S
authors.lastname: Sadallah
authors.forename: F
authors.initials: F
authors.lastname: Gudat
authors.forename: M J
authors.initials: MJ
authors.lastname: Mihatsch
authors.forename: J A
authors.initials: JA
authors.lastname: Schifferli
mesh_terms: D000911:Antibodies, Monoclonal; D004847:Epithelial Cells / Q000378:metabolism; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000378:metabolism / Q000473:pathology; D009393:Nephritis / Q000378:metabolism / Q000473:pathology; D009402:Nephrosis, Lipoid / Q000378:metabolism / Q000473:pathology; D017463:Receptors, Complement 3b / Q000378:metabolism*; D012016:Reference Values
chemical_list: D000911:Antibodies, Monoclonal; D017463:Receptors, Complement 3b