Autoantibody-mediated desialylation impairs human thrombopoiesis and platelet lifespan

Immune thrombocytopenia is a common bleeding disease caused by autoantibody-mediated accelerated platelet clearance and impaired thrombopoiesis. Accumulating evidence suggests that desialylation affects platelet lifespan in immune thrombocytopenia. Herein, we report on novel effector functions of autoantibodies from patients with immune thrombocytopenia, which might interfere with the clinical picture of the disease. Data from our study show that a subgroup of autoantibodies is able to induce cleavage 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 an ex vivo model of thrombopoiesis, a humanized animal model, and a clinical cohort study, we demonstrate that cleavage of sialic acid induces significant impairment of the 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.

Automated summary

In this study, novel effector functions of autoantibodies in patients with immune thrombocytopenia were identified, which interfere with the clinical presentation of the disease by inducing cleavage of sialic acid residues from the surface of platelets and megakaryocytes. Additionally, desialylation mediated by autoantibodies disrupts the interaction between cells and extracellular matrix proteins, leading to impaired platelet adhesion and megakaryocyte differentiation. This suggests that prevention of desialylation may be a potential therapeutic approach in the future clinical studies for treating bleeding in immune thrombocytopenia.