title: Mesangial IgA1 in IgA nephropathy exhibits aberrant O-glycosylation: observations in three patients.
abstract: BACKGROUND
  In IgA nephropathy (IgAN), circulating IgA1 molecules display an abnormal pattern of O-glycosylation. This abnormality may potentially contribute to mesangial IgA1 deposition, but this is unproven because the O-glycosylation of mesangial IgA1 has not been analyzed.
  
  
  METHODS
  IgA1 was eluted from glomeruli isolated from the kidneys of three IgAN patients obtained after nephrectomy or at postmortem. Serum from these patients, other patients with IgAN, and controls was subjected to the same treatment as the glomerular eluates. The O-glycosylation of eluted and serum IgA1 was measured by lectin binding using an enzyme-linked immunosorbent assay-based system.
  
  
  RESULTS
  In all three cases, the lectin binding of IgA1 eluted from the glomeruli of IgAN patients was markedly higher than that of the serum IgA1 of the same individual, and also all but one of a series of serum IgA1 samples from other patients and controls.
  
  
  CONCLUSIONS
  The higher lectin binding of glomerular compared with serum IgA1 suggests that O-glycosylated IgA1 molecules abnormally and selectively deposit in the kidney. These results provide the first evidence that mesangial IgA1 is abnormally O-glycosylated, and support a direct role for abnormal IgA1 O-glycosylation in the mechanism of mesangial IgA deposition in IgAN.
authors.affiliation: Department of Nephrology, Leicester General Hospital, Leicester, England, United Kingdom. aa50@le.ac.uk
authors.forename: A C
authors.initials: AC
authors.lastname: Allen
authors.forename: E M
authors.initials: EM
authors.lastname: Bailey
authors.forename: P E
authors.initials: PE
authors.lastname: Brenchley
authors.forename: K S
authors.initials: KS
authors.lastname: Buck
authors.forename: J
authors.initials: J
authors.lastname: Barratt
authors.forename: J
authors.initials: J
authors.lastname: Feehally
mesh_terms: D000328:Adult; D001344:Autopsy; D005920:Glomerular Mesangium / Q000737:chemistry / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000737:chemistry*; D007674:Kidney Diseases / Q000097:blood / Q000276:immunology*; D037102:Lectins; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy
chemical_list: D007070:Immunoglobulin A; D037102:Lectins