The Importance of Platelet Glycoside Residues in the Haemostasis of Patients with Immune Thrombocytopaenia.

Andrés Ramírez-López,Sara García Barcenilla,Víctor Jiménez Yuste,Paula Acuña,Raul Justo Sanz,Nora V Butta,María Isabel Rivas Pollmar,Elena G Arias-Salgado,María Teresa Álvarez Román,Mónica Martín Salces,Tamara Cebanu,Elena González Zorrilla,Elena Monzón Manzano

doi:10.3390/jcm10081661

Andrés Ramírez-López, Sara García Barcenilla + Show 11 more

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https://doi.org/10.3390/jcm10081661

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Abstract

Loss of sialic acid from the carbohydrate side chains of platelet glycoproteins can affect platelet clearance, a proposed mechanism involved in the etiopathogenesis of immune thrombocytopaenia (ITP). We aimed to assess whether changes in platelet glycosylation in patients with ITP affected platelet counts, function, and apoptosis. This observational, prospective, and transversal study included 82 patients with chronic primary ITP and 115 healthy controls. We measured platelet activation markers and assayed platelet glycosylation and caspase activity, analysing samples using flow cytometry. Platelets from patients with ITP with a platelet count <30 × 103/µL presented less sialic acid. Levels of α1,6-fucose (a glycan residue that can directly regulate antibody-dependent cellular cytotoxicity) and α-mannose (which can be recognised by mannose-binding-lectin and activate the complement pathway) were increased in the platelets from these patients. Platelet surface exposure of other glycoside residues due to sialic acid loss inversely correlated with platelet count and the ability to be activated. Moreover, loss of sialic acid induced the ingestion of platelets by human hepatome HepG2 cells. Changes in glycoside composition of glycoproteins on the platelets’ surface impaired their functional capacity and increased their apoptosis. These changes in platelet glycoside residues appeared to be related to ITP severity.

Highlights

Introduction published maps and institutional affilImmune thrombocytopaenia (ITP) is an autoimmune disease characterised by a low platelet count (≤100 × 109 /L) due to platelet destruction and insufficient platelet production [1]
As expected, expected, we found a direct relationship between neuraminidase activity in serum and binding we found a direct relationship between neuraminidase activity in serum and Ricinus communis agglutinin (RCA) binding to platelets
We demonstrated that platelets with the lowest exposure of sialic acid were the most ingested by human that platelets with the lowest exposure of sialic acid were the most ingested by human hepatome HepG2 cells

Summary

Introduction

Immune thrombocytopaenia (ITP) is an autoimmune disease characterised by a low platelet count (≤100 × 109 /L) due to platelet destruction and insufficient platelet production [1]. ITP is considered a rare disease (ORPHA 3002, OMIM 188030) that is diagnosed by ruling out other causes of thrombocytopaenia. The initial event leading to antiplatelet autoimmunity remains unclear [2]; there is strong evidence that autoantibodies and autoreactive CD8+ cytotoxic T cells trigger enhanced platelet destruction and impair platelet production by megakaryocytes in the bone marrow [3]. ITP has been described as a deterioration of the regulatory compartment (regulatory T [Treg] and regulatory B [Breg] cells) of these patients’ immune system [4], along with a polarisation of the response towards T helper 1 (Th1) and Th17 cells. The abnormal T-cell function leads to the proliferation and differentiation of self-reactive B cells [5]. iations.

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