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

Kapur, RickAcademic Medical Center of University of Amsterdam (AMC),University of Amsterdam (författare)

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.

Aslam, RukhsanaSaint Michael's Hospital (författare)
Speck, Edwin R.Saint Michael's Hospital (författare)
Rebetz, Johan M.Lund University,Lunds universitet,Trombocyt immunologi,Forskargrupper vid Lunds universitet,Platelet Immunology,Lund University Research Groups(Swepub:lu)wbla-jre (författare)
Semple, John W.Lund University,Lunds universitet,Trombocyt immunologi,Forskargrupper vid Lunds universitet,Platelet Immunology,Lund University Research Groups,University of Toronto,Saint Michael's Hospital(Swepub:lu)jo0201se (författare)
Academic Medical Center of University of Amsterdam (AMC)University of Amsterdam (creator_code:org_t)

Av författaren/redakt...: Kapur, Rick; Aslam, Rukhsana; Speck, Edwin R.; Rebetz, Johan M.; Semple, John W.

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Hematologi

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