Platelet desialylation correlates with efficacy of first-line therapies for immune thrombocytopenia
نویسندگان
چکیده
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.
منابع مشابه
CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia
In addition to antiplatelet autoantibodies, CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8(+) T cells induce platelet desialylation in ITP remains unclear. H...
متن کاملClinical Significance of Positive Platelet Immunofluorescence Assay in Adult Immune Thrombocytopenia: a Cross Sectional Study
Background: Immune thrombocytopenia is a hematologic disorder characterized by low platelet count and variable bleeding manifestations due to immune-mediated platelet destruction and/or suppression of platelet production. This study was performed to evaluate characteristics and clinical presentations of adult patients with immune thrombocytopenia and to explore the clinical value of platelet an...
متن کاملDesialylation is a mechanism of Fc-independent platelet clearance and a therapeutic target in immune thrombocytopenia
Immune thrombocytopenia (ITP) is a common bleeding disorder caused primarily by autoantibodies against platelet GPIIbIIIa and/or the GPIb complex. Current theory suggests that antibody-mediated platelet destruction occurs in the spleen, via macrophages through Fc-FcγR interactions. However, we and others have demonstrated that anti-GPIbα (but not GPIIbIIIa)-mediated ITP is often refractory to t...
متن کاملSevere platelet desialylation in a patient with glycoprotein Ib/IX antibody-mediated immune thrombocytopenia and fatal pulmonary hemorrhage.
متن کامل
Sunitinib Induced Immune Thrombocytopenia
Sunitinib is an oral tyrosine kinase inhibitor which prevents tumor growth and metastatic progression. It was approved for treatment of advanced renal cell cancer, gastrointestinal stromal tumor and advanced pancreatic neuroendocrine tumors. It has several adverse reactions on multi organ systems including hematologic system. Although the neutropenia and thrombocytopenia commonly happens as Gra...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
دوره 10 شماره
صفحات -
تاریخ انتشار 2017