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Asparaginase Immune Complexes Induce FcγRIII‐Dependent Basophil Activation and Concentration‐Dependent Hypersensitivity Reactions

Asparaginase (ASNase) is an important drug for treatment of pediatric acute lymphoblastic leukemia. However, antibody responses to ASNase increase the risk of leukemia relapse by mediating ASNase‐induced hypersensitivity and blocking ASNase's therapeutic effects. Previously, we have demonstrated two mechanism of ASNase hypersensitivity: one involving an anti‐ASNase IgG response, and another involving cell‐associated anti‐ASNase IgE antibodies. These studies suggested that formation of ASNase immune complexes (ICs) is sufficient to induce ASNase hypersensitivity.