Differential recognition of diet-derived Neu5Gc-Neoantigens on glycan microarrays by carbohydrate-specific pooled human IgG and IgA antibodies

Shani Leviatan Ben-Arye, Christoph Schneider, Hai Yu, Salam Bashir, Xi Chen, Stephan Von Gunten, Vered Padler-Karavani*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish
Pages (from-to)1565-1574
Number of pages10
JournalBioconjugate Chemistry
Volume30
Issue number5
DOIs
StatePublished - 15 May 2019

Funding

FundersFunder number
European Union H2020 ProgramERC-2016-STG-716220
Horizon 2020 Framework Programme716220
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung310030_162552, 310030_184757
Swiss Cancer Research FoundationKFS-3941-08-2016

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