Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP)
Kapur, Rick LU ; Aslam, Rukhsana ; Speck, Edwin R. ; Rebetz, Johan M. LU
and Semple, John W.
LU
(2020)
In Platelets
31(3).
p.399-402
- 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... (More)
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.
(Less)
- author
- Kapur, Rick
LU
; Aslam, Rukhsana
; Speck, Edwin R.
; Rebetz, Johan M.
LU
and Semple, John W.
LU
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Immune thrombocytopenia (ITP), immunomodulation, platelet antibodies, platelet counts, thrombopoietin receptor agonist (TPO-RA)
- in
- Platelets
- volume
- 31
- issue
- 3
- pages
- 4 pages
- publisher
- Taylor & Francis
- external identifiers
-
- pmid:31146647
- scopus:85066623546
- ISSN
- 0953-7104
- DOI
- 10.1080/09537104.2019.1624709
- language
- English
- LU publication?
- yes
- id
- f845d38a-c511-472a-9bff-92630ca9115c
- date added to LUP
- 2019-06-25 12:53:49
- date last changed
- 2024-04-02 07:54:43
@article{f845d38a-c511-472a-9bff-92630ca9115c,
abstract = {{<p>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.</p>}},
author = {{Kapur, Rick and Aslam, Rukhsana and Speck, Edwin R. and Rebetz, Johan M. and Semple, John W.}},
issn = {{0953-7104}},
keywords = {{Immune thrombocytopenia (ITP); immunomodulation; platelet antibodies; platelet counts; thrombopoietin receptor agonist (TPO-RA)}},
language = {{eng}},
number = {{3}},
pages = {{399--402}},
publisher = {{Taylor & Francis}},
series = {{Platelets}},
title = {{Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP)}},
url = {{http://dx.doi.org/10.1080/09537104.2019.1624709}},
doi = {{10.1080/09537104.2019.1624709}},
volume = {{31}},
year = {{2020}},
}