title: Epidermal basement membrane alpha 5(IV) expression in females with Alport syndrome and severity of renal disease.
abstract: BACKGROUND
  X-linked Alport syndrome is a progressive nephritis caused by mutations of the COL4A5 gene. This gene encodes the collagen alpha 5(IV) chain, which is abnormally distributed in the glomerular basement membrane (GBM) and epidermal basement membrane (EBM). It has been reported a negative correlation between alpha 5(IV) chain distribution in EBM and the degree of proteinuria in heterozygous females with Alport syndrome.
  
  
  METHODS
  In the present study, we evaluated the distribution of the alpha 5(IV) chain in the EBM and the degree of proteinuria in 22 females with X-linked Alport syndrome. The distribution of the cutaneous alpha 5(IV) chain was measured by a confocal laser microscope using an anti-alpha 5(IV) monoclonal antibody. The expression ratio of alpha 5(IV) distribution was quantified dividing the extension of the positive signal and the maximal extension of the specimen. Urinary protein excretion was expressed as urinary protein over urinary creatinine ratio.
  
  
  RESULTS
  Proteinuria was present in five of the 22 patients. In two patients with proteinuria, alpha 5(IV)chain was normally distributed; in the remaining three, the expression ratio of alpha 5(IV)chain was 35%, 47%, and 48%. Of the 17 patients without proteinuria, two displayed a complete absence of the alpha 5(IV) chain in EBM, five displayed a normal staining, and the remaining 10 had an expression ratio between 18% and 65%.
  
  
  CONCLUSIONS
  Our data suggest that there is no correlation between the severity of the glomerular involvement (expressed by proteinuria) and the staining of the alpha 5 chain in the EBM in females with X-linked Alport syndrome.
authors.affiliation: Division of Nephrology and Dialysis, Bambino Gesù Children's Hospital and Research Institute, Rome, Italy. lmassella@opbg.net
authors.forename: Laura
authors.initials: L
authors.lastname: Massella
authors.forename: Andrea
authors.initials: A
authors.lastname: Onetti Muda
authors.forename: Tullio
authors.initials: T
authors.lastname: Faraggiana
authors.forename: Cristiano
authors.initials: C
authors.lastname: Bette
authors.forename: Alessandra
authors.initials: A
authors.lastname: Renieri
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Rizzoni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001485:Basement Membrane / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024141:Collagen Type IV / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism; D008875:Middle Aged; D009394:Nephritis, Hereditary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D010375:Pedigree; D011507:Proteinuria / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: C478159:COL4A5 protein, human; D024141:Collagen Type IV