Abstract Number: PB0883
Meeting: ISTH 2021 Congress
Background: Immune thrombocytopenia (ITP) is an autoimmune disease characterised by a low platelet count with a deterioration of the regulatory compartment (regulatory T [Treg] and regulatory B [Breg] cells). Nevertheless the initial event leading to antiplatelet autoimmunity remains unclear.
Aims: The aim of our study was to analyse the role of sialic acid of platelet glycoproteins to better understand their role in platelet function and in the development of ITP.
Methods: This observational, prospective and transversal study included 82 patients with chronic primary ITP and 115 healthy controls. Our local Ethics Committee approved the protocol, and participants signed informed consent.
Platelet activation markers, loss of sialic acid (binding of Ricinus comunnis agglutinin, RCA), caspase activity; and detection of peripheral blood mononuclear cells subsets, were evaluated by flow cytometry.
Neuraminidase (NEU) activity in serum was determined with the substrate 20-(4-methylumbelliferyl)-a-D-N- (MUNANA).
Results: Loss of sialic acid from platelet surface was a key player for reducing platelet count (Figure 1A) and platelet’s capacity of activation, as shown by the negative correlation between RCA binding and ability of fibrinogen receptor to be activated (PAC1 binding) and agonist-induced degranulation (P-selectin and CD63 exposure, Figure 1B) with TRAP. Loss of sialic acid was accompanied by increased platelet caspase activities(Figure 1C).
Loss of sialic acid from platelet surface was due to the enhancement of neuraminidase activity in patients with ITP (Figure 2A). ITP patients with the lowest exposure of sialic acid showed the most pronounced decrease in LTregand the higher plasmablasts count (Figure 2B).
Conclusions: Loss of sialic acid from platelets induced an impairment of their ability to be activated and an increased apoptosis, accompanied by a diminished LTreg population and a higher plasmablast subset. These observations posited loss of sialic from platelets as aetiopathogenic agents in ITP.
Research funded by FIS-Fondos FEDER PI19/00772 and Platelet Disorder Support Association
To cite this abstract in AMA style:Butta Coll NV, Álvarez Román MT, Monzón Manzano E, Martín Salces M, Rivas Pollmar MI, García Arias-Salgado E, Acuña P, García Barcenilla S, González Zorrilla E, Cebanu T, Jiménez Yuste V. Importance of Platelet’s Sialic Acid Residues on Haemostasis and Immune System of Patients with Immune Thrombocytopenia [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/importance-of-platelets-sialic-acid-residues-on-haemostasis-and-immune-system-of-patients-with-immune-thrombocytopenia/. Accessed September 16, 2021.
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