Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP)

Abstract

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which autoantibodies and/or autoreactive T cells destroy platelets and megakaryocytes in the spleen and bone marrow, respectively. Thrombopoietin receptor agonists (TPO-RA e.g. Romiplostim and Eltrombopag) have made a substantial contribution to the treatment of patients with ITP, which are refractory to first-line treatments and approximately 30% demonstrate sustained elevated platelet counts after drug tapering. How TPO-RA induce these sustained responses is not known. We analyzed the efficacy of a murine TPO-RA in a well-established murine model of active ITP. Treatment with TPO-RA (10 ug/kg, based on pilot dose escalation experiments) significantly raised the platelet counts in ITP-mice. Immunomodulation was assessed by measuring serum IgG anti-platelet antibody levels; TPO-RA-treated mice had significantly reduced IgG anti-platelet antibodies despite the increasing platelet counts. These results suggest that TPO-RA is not only an efficacious therapy but also reduces anti-platelet humoral immunity in ITP.

KEYWORDS:

• Immune thrombocytopenia (ITP)
• immunomodulation
• platelet antibodies
• platelet counts
• thrombopoietin receptor agonist (TPO-RA)

Acknowledgements

We thank Amgen for graciously supplying the murine TPO-RA (AMP4).

Declaration of interest statement

The authors report no potential conflicts of interest.

Author’s contributions

R.K. and R.A. designed and performed experiments, collected, analyzed, interpreted data, wrote and edited the paper; E.R.S performed experiments and collected data; J.M.R. collected and interpreted data; J.W.S. provided financial resources and edited the manuscript.

Additional information

Funding

This work was supported by grants from Health Canada and Canadian Blood Services.