Hypersensitivity reactions to asparaginase in mice are mediated by anti-asparaginase IgE and IgG and the immunoglobulin receptors Fc ϵRI and FcγRIII.

Hypersensitivity reactions to asparaginase in mice are mediated by anti-asparaginase IgE and IgG and the immunoglobulin receptors FcϵRI and FcγRIII.
Haematologica. 2018 Sep 20;:
Authors: Rathod S, Ramsey M, Relling MV, Finkelman FD, Fernandez CA
Abstract
Asparaginase is an important drug for the treatment of leukemias. However, anti-asparaginase antibodies often develop, which can decrease asparaginase drug levels and increase the risk of relapse. The aim of this study is to identify the immunoglobulin isotypes and receptors responsible for asparaginase hypersensitivities. Mice immunized with asparaginase developed anti-asparaginase IgG1 and IgE antibodies, and challenging the sensitized mice with asparaginase induced severe hypersensitivity reactions. Flow cytometry analysis indicated that macrophages/monocytes, neutrophils, and basophils bind asparaginase ex vivo through FcγRIII. In contrast, asparaginase binding to basophils was dependent on FcγRIII and IgE. Consistent with the asparaginase binding data, basophil activation by asparaginase occurred via both IgG/FcγRIII and IgE/FcϵRI. Depleting >95% of B cells suppressed IgG but not IgE-dependent hypersensitivity, while depleting CD4+ T cells provided complete protection. Combined treatment with either anti-IgE mAb plus a platelet-activating factor receptor antagonist or anti-FcγRIII mAb plus a H1 receptor antagonist suppressed asparaginase hypersensitivity. The observati...

Source: Haematologica - September 20, 2018 Category: Hematology Authors: Rathod S, Ramsey M, Relling MV, Finkelman FD, Fernandez CA Tags: Haematologica Source Type: research