{"doi":"10.3389/fimmu.2023.1233356","title":"Factor VIII antibody immune complexes modulate the humoral response to factor VIII in an epitope-dependent manner","abstract":"Introduction Soluble antigens complexed with immunoglobulin G (IgG) antibodies can induce robust adaptive immune responses in vitro and in animal models of disease. Factor VIII immune complexes (FVIII-ICs) have been detected in individuals with hemophilia A and severe von Willebrand disease following FVIII infusions. Yet, it is unclear if and how FVIII-ICs affect antibody development over time. Methods In this study, we analyzed internalization of FVIII complexed with epitope-mapped FVIII-specific IgG monoclonal antibodies (MAbs) by murine bone marrow-derived dendritic cells (BMDCs) in vitro and antibody development in hemophilia A (FVIII -/- ) mice injected with FVIII-IC over time. Results FVIII complexed with 2-116 (A1 domain MAb), 2-113 (A3 domain MAb), and I55 (C2 domain MAb) significantly increased FVIII uptake by BMDC but only FVIII/2-116 enhanced antibody titers in FVIII -/- mice compared to FVIII alone. FVIII/4A4 (A2 domain MAb) showed similar FVIII uptake by BMDC to that of isolated FVIII yet significantly increased antibody titers when injected in FVIII -/- mice. Enhanced antibody responses observed with FVIII/2-116 and FVIII/4A4 complexes in vivo were abrogated in the absence of the FVIII carrier protein von Willebrand factor. Conclusion These findings suggest that a subset of FVIII-IC modulates the humoral response to FVIII in an epitope-dependent manner, which may provide insight into the antibody response observed in some patients with hemophilia A.","journal":"Frontiers in Immunology","year":2023,"id":388734,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.958,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1158625,"name":"Jasmine Ito","orcid":null,"position":1,"is_corresponding":false},{"id":1158232,"name":"Elizabeth S. York","orcid":"0009-0002-9515-2252","position":2,"is_corresponding":false},{"id":402919,"name":"Courtney Cox","orcid":"0000-0001-8930-2053","position":3,"is_corresponding":false},{"id":403691,"name":"W. Hunter Baldwin","orcid":null,"position":4,"is_corresponding":false},{"id":1158626,"name":"Surinder Gill","orcid":null,"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":585344,"name":"Glaivy Batsuli","orcid":"0000-0002-0122-9320","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-19T01:18:18.214733Z","pmid":"37720212","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":[]}