Autoantibody-Mediated Desialylation Impairs Human Thrombopoiesis and Platelet Life Span

Immune thrombocytopenia (ITP) 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 ITP. Herein, we report on novel effector functions of autoantibodies from ITP patients which might interfere with the clinical picture of the disease. Data from our study show that in ITP a subgroup of autoantibodies is able to cleave sialic acid from the surface of human platelets as well as megakaryocytes.

Autoantibody-mediated receptor 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 novel findings suggest that prevention of desialylation could be a potential therapeutic approach to treat bleeding and to improve thrombopoiesis in ITP.

Publikationsverlauf

Artikel online veröffentlicht:
13. November 2020