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Glycosyltransferases Involved in the Biosynthesis of IgA O-Glycans

  • Yoshiki Narimatsu
  • Hisashi Narimatsu

Abstract

IgA nephropathy (IgAN) is a chronic inflammatory renal disease caused by the deposition of IgA1 subclass in the glomerular mesangium area, and one-third patients with IgAN could progress to end-stage renal failure. It is proposed that IgA molecules from patients with IgAN have incomplete carbohydrate chains in the O-glycan structure at the hinge region of IgA, though there is no clear evidence for this proposal. The sialyl-T (ST) antigen is a O-glycan having the following simple structure: SAα2,3Galβ1,3GalNAcα-Ser/Thr. IgA1 subclass bears at least five ST antigen in the hinge regions. It has been reported that the IgA1 molecule from the patients lacks a galactose or sialic acid residue at the end of the ST structure. The incomplete synthesis of O-glycans may induce physical change in the IgA molecule, which in turn makes IgA easy to deposit in the renal glomeruli. However, we found that only about 1% of IgA obtained from the patients contained incomplete carbohydrate chains in its molecule. Definitive diagnosis of IgAN is now being done by a renal biopsy, which imposes burden on the patients. Thus, it is required to develop novel methods for the diagnosis. Identification of glycosyltransferases involved in the biosynthesis of IgA O-glycan may lead us to elucidate cause of the disease and development of the diagnosis and therapeutic method.

Keywords

Sialic Acid Renal Biopsy Hinge Region Sialic Acid Residue Renal Glomerulus 
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.

References

  1. Iwasaki H, Zhang Y, Tachibana K, Gotoh M, Kikuchi N, Kwon YD, Togayachi A, Kudo T, Kubota T, Narimatsu H (2003) Intiation of O-glycan synthesis in IgA1 hinge region is determined by a single enzyme, UDP-N-acetyl-α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 2. J Biol Chem 278(8):5613–5621PubMedCrossRefGoogle Scholar
  2. Ju T, Cummings RD (2002) A unique molecular chaperone Cosmc required for activity of the mammalian core 1 β3-galactosyltransferase. Proc Natl Acad Sci USA 99(26):16613–16618PubMedCrossRefGoogle Scholar
  3. Ju T, Brewer K, D’Souza A, Cummings RD, Canfield WM (2002) Cloning and expression of human core 1 β1,3-galactosyltransferase. J Biol Chem 277(1):178–186PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Yoshiki Narimatsu
    • 1
  • Hisashi Narimatsu
    • 1
  1. 1.Research Center for Medical GlycosciencesNational Institute of Advanced Industrial Science and Technology (AIST)Tsukuba, IbarakiJapan

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