Antigen‐based heteropolymers: a potential therapy for binding and clearing autoantibodies via erythrocyte cr1

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Abstract
Objective. To determine if complexes containing monoclonal antibodies to CR1 cross‐linked with antigen (antigen‐based heteropolymers [AHP]) can bind the corresponding autoantibody to primate erythrocyte CR1 and promote autoantibody clearance from the circulation. Methods. AHP were constructed by cross‐linking double‐stranded DNA (dsDNA) to monoclonal antibodies to CR1. The ability of AHP to facilitate binding of human anti‐dsDNA antibodies to primate erythrocytes was studied in vitro using a variety of radioimmunoassays (including Farr assays), enzyme immunoassays, and fluorescence‐activated cell sorting. In addition, we used a monkey model to study in vivo the AHP‐mediated clearance of passively infused human anti‐dsDNA antibodies. Results. Large amounts of lupus IgG anti‐dsDNA antibodies can be specifically bound to human erythrocytes via the complexes, and studies in 2 rhesus monkeys indicate that the erythrocyte‐bound antibodies are rapidly cleared from the circulation. Conclusion. This methodology may allow for development of a new therapy to facilitate autoantibody clearance in autoimmune disease.