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Incompleteness of O-glycans at the Hinge Region of IgA1 and IgA Nephropathy

  • Hitoo Iwase
  • Yoshiyuki Hiki

Abstract

IgA nephropathy (IgAN) was first reported as a disease by Berger. The definite diagnosis of IgAN can be made by detection of deposited IgA in the glomerular mesangial region by renal biopsy. IgAN was well known as one of the most common primary glomerulonephritis forms in the world. The frequency of IgAN in renal diseases is considered to be 20–30% in Asia and Europe. Among IgAN patients, about 40% of the patients in Japan develop renal failure within 20 years. The patient is often left without treatment because the symptoms were usually slight (protein urea and episodes of hematuria). Glomerular deposited IgA was dominantly the IgA1 subclass. The disease was thought to occur due to the deposition of an immune complex. Participation of many antigens, such as a food antigen, virus and bacteria, were reported as candidates. In addition, the implication of an abnormality in the molecular structure, especially a hinge mucin-type sugar chain, of IgA1 was reported mainly based on our research results in this article (Fig. 1).

Keywords

Hinge Region Nephrol Dial Transplant IgAN Patient IgA1 Subclass IgA1 Molecule 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Hiki Y, Odani H, Takahashi M, Yasuda Y, Nishimoto A, Iwase H, Shinzato T, Kobayashi Y, Maeda K (2001) Mass spectrometry proves under O-glycosylation of glomerular IgA1 in IgA nephropathy. Kidney Int 59:1077–1085PubMedCrossRefGoogle Scholar
  2. Horie A, Hiki Y, Odani H, Yasuda Y, Takahashi M, Kato M, Iwase H, Kobayashi Y, Nakashima I, Maeda K (2003) IgA1 molecules produced by tonsillar lymphocytes are under-O-glycosylated in IgA nephropathy. Am J Kidney Dis 42:486–498PubMedCrossRefGoogle Scholar
  3. Itoh A, Iwase H, Takatani T, Nakamura I, Hayashi M, Oba K, Hiki Y, Kobayashi Y, Okamoto M (2003) Tonsillar IgA1 as a possible source of hypoglycosylated IgA in the serum of IgA nephropathy patients. Nephrol Dial Transplant 18:1108–1114PubMedCrossRefGoogle Scholar
  4. Kokubo Y, Hiki Y, Iwase H, Tanaka A, Nishikido J, Hotta K, Kobayashi Y (1999) Exposed peptide core of IgA1 hinge region in IgA nephropathy. Nephrol Dial Transplant 14:81–85PubMedCrossRefGoogle Scholar
  5. Mattu TS, Pleass RJ, Willis AC, Kilian M, Wormald MR, Lellouch AC, Rudd PN, Woof JM, Dwek RA (1998) The glycosylation and structure of human serum IgA1, Fab, and Fc regions and the role of N-glycosylation on Fc alpha receptor interactions. J Biol Chem 273:2260–2272PubMedCrossRefGoogle Scholar
  6. Nakamura I, Iwase H, Arai K, Nagai Y, Toma K, Katsunata T, Hiki Y, Kokubo T, Sano T, Kobayashi Y (2004) Detection of gender difference and epitope specificity of IgG antibody activity against IgA1 hinge portion in IgA nephropathy patients by using synthetic hinge peptide and glycopeptides probes. Nephrology 9:26–30PubMedCrossRefGoogle Scholar
  7. Odani H, Hiki Y, Takahahsi M, Nishimoto A, Yasuda Y, Iwase H, Shinzato T, Maeda K (2000) Direct evidence for decreased sialylation and galactosylation of human serum IgA1 Fc O-glycosylated hinge peptides in IgA nephropathy by mass spectrometry. Biochem Biophys Res Commun 271:268–274PubMedCrossRefGoogle Scholar
  8. Sano T, Hiki Y, Kokubo T, Iwase H, Shigematsu H, Kobayashi Y (2002) Enzymatically deglycosylated human IgA1 molecules accumulate and induce inflammatory cell reaction in rat glomeruli. Nephrol Dial Transplant 17:50–56PubMedCrossRefGoogle Scholar
  9. Takatani T, Iwase H, Itoh A, Nakamura I, Hayashi M, Sakamoto H, Kamata K, Kobayashi Y, Hiki Y, Okamoto M, Higashihara M (2004) Compositional similarity between immunoglobulins binding to asialo-, agalacto-IgA1-Sepharose and those deposited in glomeruli in IgA nephropathy. J Nephrol 17:679–686PubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Hitoo Iwase
    • 1
  • Yoshiyuki Hiki
    • 2
  1. 1.Department of BiochemistryKitasato UniversitySagamihara, KanagawaJapan
  2. 2.Division of NephrologyFujita Health UniversityAichiJapan

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