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

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.