B-cell receptor on anti-polyethylene glycol antibody-positive B-cells (APA-BCR)

The B-cell receptor (BCR) on anti-polyethylene glycol (PEG) antibody-positive B-cells (APA+ B-cells) is a membrane-bound immunoglobulin that specifically recognizes and binds to PEG polymers. These receptors are the primary mediators of the immune response against PEGylated therapeutics, such as pegloticase (Krystexxa) and PEG-asparaginase, which are used to treat conditions like chronic gout and acute lymphoblastic leukemia. When multivalent PEGylated drugs cross-link these BCRs, they trigger B-cell activation, expansion, and the subsequent secretion of high-titer anti-PEG antibodies (APA). This immune response leads to the accelerated blood clearance (ABC) of the therapeutic agent, significantly reducing its half-life and efficacy, and can also provoke severe hypersensitivity reactions or anaphylaxis. Therapeutic strategies targeting these BCRs involve the administration of high molecular weight free PEG as a decoy to saturate the receptors without causing the cross-linking necessary for activation. This approach aims to mitigate the immunogenicity of PEGylated products and restore their therapeutic profile in patients with pre-existing or induced anti-PEG immunity.

Other names

Anti-polyethylene glycol B-cell receptorAnti-PEG B-cell receptorPEG-specific B-cell receptorAPA+ B-cell receptor

Competitive inhibition of B-cell receptor cross-linking and activation by saturating receptors with monovalent or low-immunogenic free PEG polymers.