Ramírez-López Andrés, Álvarez Román María Teresa, Monzón Manzano Elena, Acuña Paula, Arias-Salgado Elena G, Martín Salces Mónica, Rivas Pollmar María Isabel, Jiménez Yuste Víctor, Justo Sanz Raul, García Barcenilla Sara, Cebanu Tamara, González Zorrilla Elena, Butta Nora V
Hematology Unit, La Paz University Hospital-IdiPAZ, Paseo de la Castellana 261, 28046 Madrid, Spain.
Medicine Faculty, Autonomous University of Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain.
J Clin Med. 2021 Apr 13;10(8):1661. doi: 10.3390/jcm10081661.
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 × 10/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.
血小板糖蛋白碳水化合物侧链上唾液酸的缺失会影响血小板清除,这是一种参与免疫性血小板减少症(ITP)发病机制的假说。我们旨在评估ITP患者血小板糖基化的变化是否会影响血小板计数、功能和凋亡。这项观察性、前瞻性和横向研究纳入了82例慢性原发性ITP患者和115例健康对照。我们测量了血小板活化标志物,检测了血小板糖基化和半胱天冬酶活性,并使用流式细胞术分析样本。血小板计数<30×10⁹/µL的ITP患者的血小板唾液酸含量较低。这些患者的血小板中α1,6-岩藻糖(一种可直接调节抗体依赖性细胞毒性的聚糖残基)和α-甘露糖(可被甘露糖结合凝集素识别并激活补体途径)水平升高。由于唾液酸缺失导致的其他糖苷残基在血小板表面的暴露与血小板计数和激活能力呈负相关。此外,唾液酸的缺失诱导人肝癌HepG2细胞吞噬血小板。血小板表面糖蛋白糖苷组成的变化损害了其功能能力并增加了其凋亡。血小板糖苷残基的这些变化似乎与ITP的严重程度有关。