Thesis Marein Schimmel
On 20 June 2017 (12:00 hrs) Marein Schimmel will defend her thesis 'Sickle cell disease: pathogenesis and biomarkers' at the University of Amsterdam
Promotores: Prof DPM Brandjes MD PhD and prof MHJ van Oers MD PhD
Copromotores: BJ Biemond PhD and prof SS Zeerleder MD PhD
Venue: Agnietenkapel, Oudezijds Voorburgwal 231, Amsterdam
Sickle cell disease (SCD) is a monogenetic disease wherein the haemoglobin complex of erythrocytes is affected, resulting in sickle haemoglobin. Sickle cell patients suffer from haemolytic anaemia, recurrent painful (micro)-vascular occlusions, secondary organ damage and early death. The pathophysiology of vaso-occlusive crises (VOC) includes neutrophil and endothelial activation, increased cellular adhesion and coagulation activation.
The aim of the research presented in this thesis was to study clinical biomarkers that may help identification of patients at risk of development of SCD related complications as these are lacking, but required to improve their clinical management.
In two of the clinical observational cohort studies that we executed, plasma levels of nucleosomes were found to have high potential to identify patients in VOC at risk of development of a serious VOC related complication, acute chest syndrome. The observed relation between levels of nucleosomes and neutrophil activation markers in plasma of patients with VOC in these studies might be an indication for the presence of Neutrophil Extracellular Traps(NET). In a subsequent experimental study we found sera of sickle cell patients able to induce NET formation in neutrophils from healthy donors. Iron chelation was effective to prevent NET formation in a subset of sickle cell sera.
In addition, this thesis includes two prospective longitudinal cohort studies in which we aimed to identify biomarkers related to the development of SCD related long-term organ complications and mortality.
Ultimately, the studies described in these thesis may help the identification of new potential targets of therapy for sickle cell patients.