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A Longitudinal Study of Glycosylation of a Human IgG3 Paraprotein in a Patient with Multiple Myeloma

  • Muhammad Farooq
  • Noriko Takahashi
  • Mark Drayson
  • John Lund
  • Royston Jefferis
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 435)

Abstract

The IgG antibody molecule is a structural paradigm for members of the immuoglobulin super family1. Whilst the oligosaccharide moiety of the IgG molecule accounts for only 23% of its mass it has been shown to be essential for optimal activation of effector mechanisms leading to the clearance and destruction of pathogens2, 3, 4. Human antibody molecules of the IgG class have N-linked oligosaccharide attached at the amide side chain of Asn-297 in the heavy chain5. The oligosaccharide moiety is of the complex bianntennary type having a heptasaccharide “core” structure (GlcNAc2Man3GlcNAc2) and variable outer arm “non-core” sugar residues, such as fucose, bisecting N-acetylglucosamine, galactose and sialic acid (Figure 1). The number of variant oligosaccharides that may be attached to heavy chains is 32 (Figure 2) and the total number of possible glycoforms >8006,7. This level of heterogeneity is evident for polyclonal IgG whilst a more restricted heterogeneity may be observed for monoclonal proteins4. In addition, ~30% of polyclonal IgG has been reported to bear a complex N- linked oligosaccharide in the Fab region8. It is apparent, therefore, that glycosylation is a post-translational modification that can introduce a very significant structural and, possibly, functional heterogeneity into the IgG molecule, such that glycoforms can alter the biological activity9.

Keywords

Multiple Myeloma Sialic Acid Plateau Phase HPLC Profile Amide Side Chain 
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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Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Muhammad Farooq
    • 1
  • Noriko Takahashi
    • 2
  • Mark Drayson
    • 1
  • John Lund
    • 1
  • Royston Jefferis
    • 1
  1. 1.Department of ImmunologyThe University of Birmingham Medical SchoolEdgbaston, BirminghamUK
  2. 2.Glycolab Nakano Vinegar CompanyHanda City 475Japan

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