Nonhuman glycans can regulate anti-factor VIII antibody formation in mice.
Animals
Antibodies
/ genetics
Antibody Formation
Blood Coagulation Factor Inhibitors
/ genetics
CHO Cells
Cricetinae
Cricetulus
Factor VIII
/ immunology
Hemophilia A
/ genetics
Mice
Mice, Knockout
Polysaccharides
/ genetics
Protein Processing, Post-Translational
/ immunology
Recombinant Proteins
/ immunology
Journal
Blood
ISSN: 1528-0020
Titre abrégé: Blood
Pays: United States
ID NLM: 7603509
Informations de publication
Date de publication:
03 03 2022
03 03 2022
Historique:
received:
17
09
2020
accepted:
06
04
2021
pubmed:
22
5
2021
medline:
16
3
2022
entrez:
21
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34019619
pii: S0006-4971(21)01106-X
doi: 10.1182/blood.2020009210
pmc: PMC8900271
doi:
Substances chimiques
Antibodies
0
Blood Coagulation Factor Inhibitors
0
Polysaccharides
0
Recombinant Proteins
0
F8 protein, human
839MOZ74GK
Factor VIII
9001-27-8
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1312-1317Subventions
Organisme : NHLBI NIH HHS
ID : U54 HL141981
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL135575
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL154034
Pays : United States
Organisme : NIH HHS
ID : DP5 OD019892
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD072245
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL141335
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2022 by The American Society of Hematology.
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