期刊
HAEMATOLOGICA
卷 107, 期 9, 页码 2195-2205出版社
FERRATA STORTI FOUNDATION
DOI: 10.3324/haematol.2021.279751
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类别
资金
- National Health and Medical Research Council [GNT 1012409]
- St. George and Sutherland Medical Research Foundation
- NSW Ministry of Health PhD Scholarship
- Research Infrastructure Program of UNSW
Immune thrombocytopenia (ITP) is a bleeding disorder caused by dysregulated B- and T- cell functions, which lead to platelet destruction. This study found that specific anti-platelet antibodies are associated with different mechanisms of thrombocytopenia, and confirmed that the NEU1 inhibitor oseltamivir can prevent platelet destruction induced by anti-GPIIb/IIIa antibodies.
Immune thrombocytopenia (ITP) is a bleeding disorder caused by dysregulated B- and T- cell functions, which lead to platelet destruction. A well-recognized mechanism of ITP pathogenesis involves anti-platelet and anti-megakaryocyte antibodies recognizing membrane glycoprotein (GP) complexes, mainly GPIb/IX and GPIIb/IIIa. In addition to the current view of phagocytosis of the opsonised platelets by splenic and hepatic macrophages via their Fc gamma receptors, antibody-induced platelet desialylation and apoptosis have also been reported to contribute to ITP pathogenesis. Nevertheless, the relationship between the specific thrombocytopenic mechanisms and various types of anti-platelet antibodies has not been established. In order to ascertain such association, we used sera from 61 ITP patients and assessed the capacity of anti-platelet antibodies to induce neuraminidase 1 (NEU1) surface expression, RCA-1 lectin binding and loss of mitochondrial inner membrane potential on donors' platelets. Sera from ITP patients with detectable antibodies caused significant platelet desialylation and apoptosis. Anti-GPIIb/IIIa antibodies appeared more capable of causing NEU1 surface translocation while anti-GPIb/IX complex antibodies resulted in a higher degree of platelet apoptosis. In ITP patients with anti-GPIIb/IIIa antibodies, both desialylation and apoptosis were dependent on Fc gamma RIIa signaling rather than platelet activation. Finally, we confirmed in a murine model of ITP that destruction of human platelets induced by anti-GPIIb/IIIa antibodies can be prevented with the NEU1 inhibitor oseltamivir. A collaborative clinical trial is warranted to investigate the utility of oseltamivir in the treatment of ITP.
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