Autoantibody-mediated desialylation impairs human thrombopoiesis and platelet lifespan.

Irene Marini, Jan Zlamal, Christoph Faul, Ursula Holzer, Stefanie Hammer, Lisann Pelzl, Wolfgang Bethge, Karina Althaus, Tamam Bakchoul

Haematologica 2021 Jan 01

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Immune thrombocytopenia is a common bleeding disease caused by autoantibody-mediated accelerated platelet clearance and impaired thrombopoiesis. Accumulating evidence suggests that desialylation affects platelet life span in immune thrombocytopenia. Herein, we report on novel effector functions of autoantibodies from immune thrombocytopenic patients which might interfere with the clinical picture of the disease. Data from our study show that a subgroup of autoantibodies is able to induce cleave of sialic acid residues from the surface of human platelets and megakaryocytes. Moreover, autoantibody-mediated desialylation interferes with the interaction between cells and extracellular matrix proteins leading to impaired platelet adhesion and megakaryocyte differentiation. Using a combination of ex vivo model of thrombopoiesis, a humanized animal model, and a clinical cohort study, we demonstrate that cleavage of sialic acid induces significant impairment in production, survival as well as function of human platelets. These data may indicate that prevention of desialylation should be investigated in the future in clinical studies as a potential therapeutic approach to treat bleeding in immune thrombocytopenia.

Citation

Irene Marini, Jan Zlamal, Christoph Faul, Ursula Holzer, Stefanie Hammer, Lisann Pelzl, Wolfgang Bethge, Karina Althaus, Tamam Bakchoul. Autoantibody-mediated desialylation impairs human thrombopoiesis and platelet lifespan. Haematologica. 2021 Jan 01;106(1):196-207