title: Serum under-galactosylated IgA1 is increased in Japanese patients with IgA nephropathy.
abstract: BACKGROUND
  Immunoglobulin A nephropathy (IgAN) is characterized by an aberrant structure of O-glycans in the IgA1 hinge region. Recently, under-galactosylated IgA1 has been found to be increased in Caucasian IgAN patients. Thus, we examined this in Japanese IgAN patients.
  
  
  METHODS
  An enzyme-linked immunosorbent assay of binding between Helix aspersa (HAA) and serum IgA was performed in Japanese IgAN patients and the HAA-IgA binding levels were compared among IgAN patients (n = 41), patients with other forms of kidney disease (OKD, n = 43) and healthy controls (n = 38). The clinicopathological severity of IgAN was then analysed between patients with high and low HAA-IgA binding levels. The levels were also compared in 11 patients before and after the combination of tonsillectomy and steroid pulse therapy. Furthermore, we examined the O-glycan structure of IgA1 hinge glycopeptides by mass spectrometry (MS).
  
  
  RESULTS
  The HAA-IgA binding levels were significantly higher in IgAN patients compared with either healthy controls (P = 0.0025) or those with OKD (P = 0.016). To reflect the absolute level of under-galactosylated IgA, we multiplied the HAA-IgA binding level by the serum IgA concentration to produce an indicative value. The specificity and sensitivity of this value were 89% and 66%, respectively. MS showed that peak distribution of IgA1 hinge glycopeptides was shifted to smaller molecular weights in high HAA-IgA-binding IgAN patients. There was no correlation between the HAA-IgA binding level and either disease severity or the use of combination therapy.
  
  
  CONCLUSIONS
  HAA-IgA binding is significantly increased in Japanese IgAN patients. This potential IgAN marker is not affected by disease severity or therapeutic intervention.
authors.affiliation: Department of Nephrology, Fujita Health University, School of Medicine, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Shimozato
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hiki
authors.forename: Hiroko
authors.initials: H
authors.lastname: Odani
authors.forename: Kazuo
authors.initials: K
authors.lastname: Takahashi
authors.forename: Kouichiro
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sugiyama
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood* / Q000175:diagnosis*; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007564:Japan; D007674:Kidney Diseases / Q000097:blood / Q000175:diagnosis; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011379:Prognosis; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D007070:Immunoglobulin A