Nonhuman glycans can regulate anti–factor VIII antibody formation in mice
| Autor: | Sooncheon Shin, Jianmei Wang, Christopher B. Doering, Shannon L. Meeks, Xeuzheng Song, Patricia E Zerra, Sean R. Stowell, Connie M. Arthur, Pete Lollar |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
0301 basic medicine
congenital hereditary and neonatal diseases and abnormalities Glycan animal diseases Immunology CHO Cells Hemophilia A Biochemistry Antibodies law.invention Mice 03 medical and health sciences chemistry.chemical_compound Cricetulus 0302 clinical medicine Polysaccharides law Cricetinae hemic and lymphatic diseases Baby hamster kidney cell Animals Mice Knockout Factor VIII Blood Coagulation Factor Inhibitors biology Immunogenicity Chinese hamster ovary cell Cell Biology Hematology Recombinant Proteins 030104 developmental biology chemistry Galactose Antibody Formation Knockout mouse Recombinant DNA biology.protein Blood Commentary Antibody Protein Processing Post-Translational 030215 immunology |
| Zdroj: | Blood |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood.2020009210 |
| Popis: | 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 α1-3 galactose (αGal) than do CHO cells, suggesting that αGal incorporation onto FVIII may result in anti-αGal antibody recognition that could positively influence the development of anti-FVIII antibodies. Consistent with this, BHK-derived FVIII exhibits increased levels of αGal, which corresponds to increased reactivity with anti-αGal antibodies. Infusion of BHK-derived, but not CHO-derived, FVIII into αGal–knockout mice, which spontaneously generate anti-αGal antibodies, results in significantly higher anti-FVIII antibody formation, suggesting that the increased levels of αGal 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|