Autoantibody-mediated platelet desialylation in ITP: the role of intracellular signaling pathways

Abstract:

Immune thrombocytopenia (ITP) is an autoimmune disorder in which the body's immune system attacks its own platelets and megakaryocytes. This leads to increased platelet clearance and reduced platelet production. Although effective treatments exist, many patients do not respond adequately, and the biological reasons for this remain poorly understood.

Recent research has uncovered that autoantibodies against platelet receptors can induce the removal of sugar molecules from platelet surfaces. This process, called desialylation, marks platelets for premature clearance in the liver, contributing to persistent thrombocytopenia and treatment resistance. Our project will investigate how desialylation is triggered and whether it can be prevented by modulating key intracellular signaling pathways downstream of platelet receptors.

Using in vivo and in vitro models, we aim to clarify how autoantibodies contribute to platelet and megakaryocyte damage and whether therapeutic modulation of these signaling cascades can restore normal platelet production, survival, and function. By linking laboratory findings to clinical data, this research will help identify which patients are most likely to benefit from targeted therapies directed at these pathways.

The expected outcome is a more precise understanding of ITP mechanisms and the foundation for personalized treatment strategies that improve platelet recovery, reduce bleeding risk, and enhance quality of life for patients living with this chronic autoimmune disease.

Short Biography:

Dr. Günalp Uzun is a clinician-scientist with a focus on transfusion medicine and platelet immunology. He graduated from medical school in Ankara, Turkey in 2001 and initially trained in hyperbaric and diving medicine, including a research fellowship at the Institute of Environmental Medicine at the University of Pennsylvania (2010-2011), where he studied the effects of hyperbaric oxygen on angiogenesis.

In 2020, he joined the Center for Clinical Transfusion Medicine at the University Hospital Tübingen, where he works under the mentorship of Prof. Dr. Tamam Bakchoul. Since June 2023, he has been supported by the Clinician Scientist Program of the German Research Foundation, which allows him to balance clinical training with dedicated research time. He is currently a consultant in transfusion medicine and directs the platelet immunology laboratory at the same department.

His research interests include understanding the mechanisms underlying immune mediated platelet disorders including immune thrombocytopenia, fetal/neonatal alloimmune thrombocytopenia, and drug-induced thrombocytopenia. Dr. Uzun has contributed to over 130 peer-reviewed publications and has been fortunate to collaborate with colleagues internationally. In addition, he is an active member of Platelet-Granulocyte Immunology Working Party of the International Society of Blood Transfusion (ISBT) and Immune-Mediated Platelet Disorders Subcommittee of International Society on Thrombosis and Hemostasis (ISTH). His work aims to improve patient outcomes by developing biomarkers that help clinicians select the most appropriate treatment for individual patients.