title: Serum under-O-glycosylated IgA1 level is not correlated with glomerular IgA deposition based upon heterogeneity in the composition of immune complexes in IgA nephropathy.
abstract: BACKGROUND
  Although serum under-O-glycosylated IgA1 in IgA nephropathy (IgAN) patients may deposit more preferentially in glomeruli than heavily-O-glycosylated IgA1, the relationship between the glomerular IgA deposition level and the O-glycan profiles of serum IgA1 remains obscure.
  
  
  METHODS
  Serum total under-O-glycosylated IgA1 levels were quantified in 32 IgAN patients by an enzyme-linked immunosorbent assay (ELISA) with Helix aspersa (HAA) lectin. Serum under-O-glycosylated polymeric IgA1 (pIgA1) was selectively measured by an original method using mouse Fcα/μ receptor (mFcα/μR) transfectant and flow cytometry (pIgA1 trap). The percentage area of IgA deposition in the whole glomeruli (Area-IgA) was quantified by image analysis on the immunofluorescence of biopsy specimens. Correlations were assessed between the Area-IgA and data from HAA-ELISA or pIgA1 trap. The relationships between clinical parameters and data from HAA-ELISA or pIgA1 trap were analyzed by data mining approach.
  
  
  RESULTS
  While the under-O-glycosylated IgA1 levels in IgAN patients were significantly higher than those in healthy controls when measured (p<0.05), there was no significant difference in under-O-glycosylated pIgA1. There was neither a correlation observed between the data from HAA-ELISA and pIgA1 trap (r2=0.09) in the IgAN patients (r2=0.005) nor was there a linear correlation between Area-IgA and data from HAA-ELISA or the pIgA1 trap (r2=0.005, 0.03, respectively). Contour plots of clinical parameters versus data from HAA-ELISA and the pIgA1 trap revealed that patients with a high score in each clinical parameter concentrated in specific areas, showing that patients with specific O-glycan profiles of IgA1 have similar clinical parameters. A decision tree analysis suggested that dominant immune complexes in glomeruli were consisted of: 1) IgA1-IgG and complements, 2) pIgA1 and complements, and 3) monomeric IgA1-IgA or aggregated monomeric IgA1.
  
  
  CONCLUSIONS
  Serum under-O-glycosylated IgA1 levels are not correlated with glomerular IgA deposition based upon heterogeneity in the composition of glomerular immune complexes in IgAN patients.
authors.forename: Kenji
authors.initials: K
authors.lastname: Satake
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. yosimizu@juntendo.ac.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Yohei
authors.initials: Y
authors.lastname: Sasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yanagawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Horikoshi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Honda
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tomino
mesh_terms: D000328:Adult; D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood* / Q000276:immunology*; D007668:Kidney / Q000276:immunology*; D008297:Male; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic
chemical_list: D000936:Antigen-Antibody Complex; D015415:Biomarkers; D007070:Immunoglobulin A; C042441:glycosylated IgA