| First Author | Batsuli G | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1233356 | PubMed ID | 37720212 |
| Mgi Jnum | J:340795 | Mgi Id | MGI:7530200 |
| Doi | 10.3389/fimmu.2023.1233356 | Citation | Batsuli G, et al. (2023) Factor VIII antibody immune complexes modulate the humoral response to factor VIII in an epitope-dependent manner. Front Immunol 14:1233356 |
| abstractText | 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. |
