Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia
Abstract Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. Despite considerable investigation, the pathogenesis of ITP remains incompletely understood, and for many patients, effective therapy is still unavailable. Using murine models and in vitro studies of human blood samples...
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| Format: | Article |
| Language: | English |
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BMC
2017-02-01
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| Series: | Journal of Hematology & Oncology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13045-017-0413-3 |
| _version_ | 1828476488240857088 |
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| author | Lili Tao Qingshu Zeng June Li Miao Xu Jiajia Wang Ying Pan Huiping Wang Qianshan Tao Yang Chen Jun Peng Ming Hou Arend Jan Gerard Jansen Heyu Ni Zhimin Zhai |
| author_facet | Lili Tao Qingshu Zeng June Li Miao Xu Jiajia Wang Ying Pan Huiping Wang Qianshan Tao Yang Chen Jun Peng Ming Hou Arend Jan Gerard Jansen Heyu Ni Zhimin Zhai |
| author_sort | Lili Tao |
| collection | DOAJ |
| description | Abstract Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. Despite considerable investigation, the pathogenesis of ITP remains incompletely understood, and for many patients, effective therapy is still unavailable. Using murine models and in vitro studies of human blood samples, we recently identified a novel Fc-independent platelet clearance pathway, whereby antibody-mediated desialylated platelets can be cleared in the liver via asialoglycoprotein receptors, leading to decreased response to standard first-line therapies targeting Fc-dependent platelet clearance. Here, we evaluated the significance of this finding in 61 ITP patients through correlation of levels of platelet desialylation with the efficacy of first-line therapies. We found that desialylation levels between different responses to treatment groups were statistically significant (p < 0.01). Importantly, correlation analysis indicated response to treatment and platelet desialylation were related (p < 0.01), whereby non-responders had significantly higher levels of platelet desialylation. Interestingly, we also found secondary ITP and certain non-ITP thrombocytopenias also exhibited significant platelet desialylation compared to healthy controls. These findings designate platelet desialylation as an important biomarker in determining response to standard treatment for ITP. Furthermore, we show for the first time platelet desialylation in other non-ITP thrombocytopenias, which may have important clinical implications and deserve further investigation. |
| first_indexed | 2024-12-11T06:29:27Z |
| format | Article |
| id | doaj.art-4f5466fcf96b4d5ab9b8415316110e83 |
| institution | Directory Open Access Journal |
| issn | 1756-8722 |
| language | English |
| last_indexed | 2024-12-11T06:29:27Z |
| publishDate | 2017-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Hematology & Oncology |
| spelling | doaj.art-4f5466fcf96b4d5ab9b8415316110e832022-12-22T01:17:33ZengBMCJournal of Hematology & Oncology1756-87222017-02-011011410.1186/s13045-017-0413-3Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopeniaLili Tao0Qingshu Zeng1June Li2Miao Xu3Jiajia Wang4Ying Pan5Huiping Wang6Qianshan Tao7Yang Chen8Jun Peng9Ming Hou10Arend Jan Gerard Jansen11Heyu Ni12Zhimin Zhai13Department of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The First Affiliated Hospital of Anhui Medical UniversityToronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science and Department of Laboratory Medicine of St. Michael’s HospitalToronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science and Department of Laboratory Medicine of St. Michael’s HospitalDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology, The First Affiliated Hospital of Anhui Medical UniversityDepartment of Hematology and Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong UniversityDepartment of Hematology and Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong UniversityDepartment of Hematology, Erasmus MCToronto Platelet Immunobiology Group, Keenan Research Centre for Biomedical Science and Department of Laboratory Medicine of St. Michael’s HospitalDepartment of Hematology, The Second Affiliated Hospital of Anhui Medical UniversityAbstract Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder. Despite considerable investigation, the pathogenesis of ITP remains incompletely understood, and for many patients, effective therapy is still unavailable. Using murine models and in vitro studies of human blood samples, we recently identified a novel Fc-independent platelet clearance pathway, whereby antibody-mediated desialylated platelets can be cleared in the liver via asialoglycoprotein receptors, leading to decreased response to standard first-line therapies targeting Fc-dependent platelet clearance. Here, we evaluated the significance of this finding in 61 ITP patients through correlation of levels of platelet desialylation with the efficacy of first-line therapies. We found that desialylation levels between different responses to treatment groups were statistically significant (p < 0.01). Importantly, correlation analysis indicated response to treatment and platelet desialylation were related (p < 0.01), whereby non-responders had significantly higher levels of platelet desialylation. Interestingly, we also found secondary ITP and certain non-ITP thrombocytopenias also exhibited significant platelet desialylation compared to healthy controls. These findings designate platelet desialylation as an important biomarker in determining response to standard treatment for ITP. Furthermore, we show for the first time platelet desialylation in other non-ITP thrombocytopenias, which may have important clinical implications and deserve further investigation.http://link.springer.com/article/10.1186/s13045-017-0413-3PlateletImmune thrombocytopeniaAntibodyDesialylationSteroid and IVIG therapy |
| spellingShingle | Lili Tao Qingshu Zeng June Li Miao Xu Jiajia Wang Ying Pan Huiping Wang Qianshan Tao Yang Chen Jun Peng Ming Hou Arend Jan Gerard Jansen Heyu Ni Zhimin Zhai Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia Journal of Hematology & Oncology Platelet Immune thrombocytopenia Antibody Desialylation Steroid and IVIG therapy |
| title | Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia |
| title_full | Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia |
| title_fullStr | Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia |
| title_full_unstemmed | Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia |
| title_short | Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia |
| title_sort | platelet desialylation correlates with efficacy of first line therapies for immune thrombocytopenia |
| topic | Platelet Immune thrombocytopenia Antibody Desialylation Steroid and IVIG therapy |
| url | http://link.springer.com/article/10.1186/s13045-017-0413-3 |
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