{"doi":"10.1182/blood.2020009210","title":"Nonhuman glycans can regulate anti–factor VIII antibody formation in mice","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.","journal":"Blood","year":2021,"id":173428,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":402915,"name":"Patricia E. Zerra","orcid":"0000-0003-3675-2725","position":1,"is_corresponding":false},{"id":403690,"name":"Sooncheon Shin","orcid":null,"position":2,"is_corresponding":false},{"id":693548,"name":"Jianmei Wang","orcid":"0000-0003-2811-4344","position":3,"is_corresponding":false},{"id":712134,"name":"Xeuzheng Song","orcid":null,"position":4,"is_corresponding":false},{"id":380170,"name":"Christopher B. Doering","orcid":"0000-0002-5662-0060","position":5,"is_corresponding":false},{"id":409323,"name":"Pete Lollar","orcid":"0000-0002-1206-8104","position":6,"is_corresponding":false},{"id":402921,"name":"Shannon L. Meeks","orcid":"0000-0002-3683-8644","position":7,"is_corresponding":false},{"id":226169,"name":"Sean R. Stowell","orcid":"0000-0002-1130-9551","position":8,"is_corresponding":false},{"id":226163,"name":"Connie M. Arthur","orcid":"0009-0006-9246-7231","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-18T23:46:49.903770Z","pmid":"34019619","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}