Anti-GalNAcα (anti-Tn) antibody repertoire differs between individuals with blood groups A and B

Recently, Breiman et al. (2021) reported that the level of anti-Tn in the blood of healthy donors and COVID-19 patients is significantly lower in individuals of blood group A than B. This prompted us to look for qualitative differences in the repertoire of anti-Tn like specificity in individuals of different blood groups (BG). To this end, we isolated antibodies from the pooled sera of BG A and BG B healthy donors using GalNAcα-sepharose, followed by Printed Glycan Array analysis. As expected, antibodies affinity isolated from BG A donors completely lack species directed to canonical (GalNAcα-transferase dependent) A-glycans, such as A (types 1, 2 and 4), GalNAcα1-3(Fucα1-2)Gal, GalNAcα1-3Galβ1-4GlcNAc (linear A), and ALe^Y. Unexpectedly, GalNAcα1-4Galβ1-4GlcNAc, glycan with an unnatural 1-4 bond fell into the same group, i.e., antibodies to it were found only in BG B donors. Other unexpected results include the following: (1) for GalNAcα1-OCH₂CH(COOH)NH₂ (GalNAcα-OSer, immobilized by NH₂ group) the opposite result was observed, i.e. affinity isolated anti-Tn antibodies of BG A donors demonstrated significantly higher titer than of BG B; (2) in BG A donors, the level of antibodies to GalNGcα1-3GalNAcα (i.e. disaccharide in N-glycolyl form) is close to background, while there is a significant level of these antibodies in the BG B donors. Since antiglycan antibodies are known to play both a protective role in antimicrobial immunity and to promote infectivity, the knowledge gained about the difference in the specificity profiles of anti-Tn antibodies signals the need to take blood group into account in developing therapeutic strategies.