Abstract

Using a murine model of ITP, we have previously demonstrated that both IVIg and a monoclonal antibody which reacts with red cells (TER-119), ameliorates thrombocytopenia. We have also recently demonstrated that passive transfer of IVIg-primed splenic leukocytes can completely recapitulate the effects of standard IVIg therapy in the amelioration of murine ITP, and further showed that CD11c+ dendritic cells were the primary cell mediating IVIg functions (

Nat Med
2006
;
12
:
688
–692
). However, the duration of action of IVIg, TER-119 and IVIg-primed leukocytes in the inhibition of murine ITP has not been evaluated. Herein, we have evaluated the efficacy and duration of action of IVIg-primed leukocytes compared with standard therapeutic delivery of IVIg and TER-119. On day 1, mice were pre-treated with 50 ug TER-119 or 50 mg IVIg, or with only 106 leukocytes that had been primed for 30 minutes with IVIg, followed by extensive washing to remove all extraneous IVIg. Alternatively, leukocytes were also primed as above with BSA as a negative control. On days 2, 5, 8 and 11, mice from each group were injected with an antibody directed to integrin αIIβ to induce immune thrombocytopenia and bled the following day for platelet enumeration. On days 3 and 6, platelet counts revealed that mice receiving IVIg-primed leukocytes, IVIg or TER-119 were all protected from thrombocytopenia to the same extent. Mice that were pre-treated with leukocytes primed with BSA were not protected, as expected. However, at day 9, mice that received IVIg-primed leukocytes were still completely protected from thrombocytopenia, while mice receiving IVIg or TER-119 were not protected. By day 12, none of the treatment regimens conferred protection from thrombocytopenia. We are currently repeating these experiments with IVIg-primed bone marrow-derived dendritic cells and these results will also be presented. These data confirm that in the treatment of murine immune thrombocytopenia, pre-treatment of mice with IVIg-primed leukocytes offers up to 50% longer duration of protection from thrombocytopenia than standard therapies with IVIg or TER-119.

Disclosure: No relevant conflicts of interest to declare.

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