Anti-factor VIII alloantibody B cell receptor (FVIII-BCR) (FVIII-BCR)

The Anti-factor VIII alloantibody B cell receptor (FVIII-BCR) is a membrane-bound immunoglobulin expressed on the surface of pathogenic B cells in patients with Hemophilia A. In these patients, the immune system recognizes therapeutic Factor VIII replacement as a foreign protein, leading to the development of neutralizing alloantibodies known as inhibitors (Meeks & Batsuli, 2016). The FVIII-BCR is responsible for recognizing FVIII, triggering B cell activation, and subsequent differentiation into antibody-secreting plasma cells. Targeting this specific BCR allows for the selective elimination of the B cell clones responsible for inhibitor production without causing broad immunosuppression (Zhang et al., 2019). Current therapeutic strategies under investigation include Chimeric Antigen Receptor (CAR) T-cells and B-cell Antibody Receptor (BAR) T-cells that utilize FVIII domains to specifically bind and destroy these pathogenic B cells (Parvathaneni & Scott, 2021). This precision medicine approach aims to restore the efficacy of FVIII replacement therapy and improve clinical outcomes for hemophilia patients with high-titer inhibitors. Additionally, research into CAR-Treg cells targeting the FVIII-BCR seeks to induce long-term immune tolerance rather than just cell depletion.

Other names

Factor VIII-specific B cell receptorFVIII-specific BCRAnti-FVIII BCRFactor VIII-specific membrane immunoglobulin

Selective depletion of pathogenic B cells expressing receptors specific for Factor VIII through targeted cytotoxicity or induction of immune tolerance.