| First Author | Arthur CM | Year | 2022 |
| Journal | Blood | Volume | 139 |
| Issue | 9 | Pages | 1312-1317 |
| PubMed ID | 34019619 | Mgi Jnum | J:322770 |
| Mgi Id | MGI:7260019 | Doi | 10.1182/blood.2020009210 |
| Citation | Arthur CM, et al. (2022) Nonhuman glycans can regulate anti-factor VIII antibody formation in mice. Blood 139(9):1312-1317 |
| abstractText | Recombinant factor VIII (FVIII) products represent a life-saving intervention for patients with hemophilia A. However, patients can develop antibodies against FVIII that prevent its function and directly increase morbidity and mortality. The development of anti-FVIII antibodies varies depending on the type of recombinant product used, with previous studies suggesting that second-generation baby hamster kidney (BHK)-derived FVIII products display greater immunogenicity than do third-generation Chinese hamster ovary (CHO)-derived FVIII products. However, the underlying mechanisms responsible for these differences remain incompletely understood. Our results demonstrate that BHK cells express higher levels of the nonhuman carbohydrate alpha1-3 galactose (alphaGal) than do CHO cells, suggesting that alphaGal incorporation onto FVIII may result in anti-alphaGal antibody recognition that could positively influence the development of anti-FVIII antibodies. Consistent with this, BHK-derived FVIII exhibits increased levels of alphaGal, which corresponds to increased reactivity with anti-alphaGal antibodies. Infusion of BHK-derived, but not CHO-derived, FVIII into alphaGal-knockout mice, which spontaneously generate anti-alphaGal antibodies, results in significantly higher anti-FVIII antibody formation, suggesting that the increased levels of alphaGal on BHK-derived FVIII can influence immunogenicity. These results suggest that posttranslational modifications of recombinant FVIII products with nonhuman carbohydrates may influence the development of anti-FVIII antibodies. |
