Nonhuman Glycans Can Regulate Anti-factor VIII Antibody Formation in Mice

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2021 May 21

PMID 34019619

Citations 13

Authors

Connie M Arthur

Patricia E Zerra

Sooncheon Shin

Jianmei Wang

Xeuzheng Song

Christopher B Doering

Pete Lollar

Shannon Meeks

Sean R Stowell

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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The role of glycosylation in clinical allergy and immunology.

Hale R, Morais D, Chou J, Stowell S J Allergy Clin Immunol. 2023; 153(1):55-66.

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