title: Oxidative stress and galactose-deficient IgA1 as markers of progression in IgA nephropathy.
abstract: OBJECTIVE
  We assessed the activation of the oxidative stress pathway in patients with IgA nephropathy (IgAN), while evaluating the classic marker of the disease (galactose-deficient serum IgA1).
  
  
  METHODS
  Sera from 292 patients and 69 healthy controls from Italy and the United States were assayed for advanced oxidation protein products (AOPPs), free sulfhydryl groups on albumin (SH-Alb), and IgA1 with galactose-deficient hinge-region O-glycans (Gd-IgA1). Gd-IgA1 was detected by binding to Helix aspersa agglutinin (HAA) and expressed as total Gd-IgA1 or as degree of galactose deficiency relative to a standard Gd-IgA1 myeloma protein (%HAA).
  
  
  RESULTS
  Sera from IgAN patients showed higher levels of Gd-IgA1, %HAA, and AOPPs, but lower levels of SH-Alb in comparison to that from healthy controls. Serum levels of AOPPs significantly correlated with serum Gd-IgA1 and %HAA. The relationship between these biomarkers and clinical features at sampling and during follow-up was assessed in 62 patients with long-term follow-up. AOPPs and %HAA correlated with proteinuria at sampling and independently associated with subsequent proteinuria. Levels of AOPPs correlated with rate of decline in renal function after sampling. The combination of a high level of AOPPs and a high level of %HAA associated with decline in estimated GFR.
  
  
  CONCLUSIONS
  Serum levels of aberrantly glycosylated IgA1 are elevated and oxidative stress pathways are activated in patients with IgAN; the intensity of the stress correlated with expression and progression of the disease. We speculate that oxidative stress may modulate the nephrotoxicity of aberrantly glycosylated IgA1 in IgAN.
authors.affiliation: Nephrology, Dialysis and Transplantation Unit, Regina Margherita Children's University Hospital, Piazza Polonia 94, 10127 Torino, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Camilla
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Valentina
authors.initials: V
authors.lastname: Daprà
authors.forename: Elisa
authors.initials: E
authors.lastname: Loiacono
authors.forename: Licia
authors.initials: L
authors.lastname: Peruzzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Amore
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Ghiggeri
authors.forename: Gianna
authors.initials: G
authors.lastname: Mazzucco
authors.forename: Francesco
authors.initials: F
authors.lastname: Scolari
authors.forename: Ali G
authors.initials: AG
authors.lastname: Gharavi
authors.forename: Gerald B
authors.initials: GB
authors.lastname: Appel
authors.forename: Stéphan
authors.initials: S
authors.lastname: Troyanov
authors.forename: Jan
authors.initials: J
authors.lastname: Novak
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Julian
authors.forename: Rosanna
authors.initials: R
authors.lastname: Coppo
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005690:Galactose / Q000097:blood* / Q000172:deficiency; D005922:Glomerulonephritis, IGA / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000097:blood; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007558:Italy; D016018:Least-Squares Analysis; D016014:Linear Models; D008297:Male; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D012709:Serum Albumin / Q000032:analysis; D013997:Time Factors; D014481:United States; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; D017127:Glycation End Products, Advanced; D007070:Immunoglobulin A; D012709:Serum Albumin; D005690:Galactose