Differential Recognition of Diet-Derived Neu5Gc-Neoantigens on Glycan Microarrays by Carbohydrate-Specific Pooled Human IgG and IgA Antibodies

Bioconjug Chem. 2019 May 15;30(5):1565-1574. doi: 10.1021/acs.bioconjchem.9b00273. Epub 2019 Apr 24.

Abstract

Sialic acids (Sias) cover vertebrate cell surface glycans. N-Acetylneuraminic acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc) are common Sia in mammals. Humans cannot synthesize Neu5Gc but accumulate it on cells through red-meat rich diets, generating numerous immunogenic Neu5Gc-neoantigens. Consequently, humans have diverse anti-Neu5Gc antibodies affecting xenotransplantation, cancer, atherosclerosis, and infertility. Anti-Neu5Gc antibodies circulate as IgG, IgM, and IgA isotypes; however, repertoires of the different isotypes in a large population have not been studied yet. Here, we used glycan microarrays to investigate anti-Neu5Gc IgGs and IgAs in intravenous immunoglobulin (IVIG) or pooled human IgA, respectively. Binding patterns on microarrays fabricated with Neu5Gc- and Neu5Ac-glycans, together with inhibition assays, revealed that different IVIG preparations have highly specific anti-Neu5Gc IgG reactivity with closely related repertoires, while IgAs show cross-reactivity against several Neu5Ac-glycans. Such different anti-Neu5Gc IgG/IgA repertoires in individuals could possibly mediate distinctive effects on human diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens / immunology*
  • Diet*
  • Humans
  • Immunoglobulin A / immunology
  • Immunoglobulin A / metabolism*
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism*
  • N-Acetylneuraminic Acid / immunology*

Substances

  • Antigens
  • Immunoglobulin A
  • Immunoglobulin G
  • N-Acetylneuraminic Acid