A novel type of macrothrombocytopenia associated with a defect in alpha2,3-sialylation
SourceAmerican Journal of Pathology, 179, 4, (2011), pp. 1969-77
Article / Letter to editor
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Laboratory of Genetic, Endocrine and Metabolic Diseases
American Journal of Pathology
SubjectDCN 1: Perception and Action IGMD 4: Glycostation disorders; DCN 3: Neuroinformatics
We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to alpha2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of alpha2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected.
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