Megakaryocyte Heterogeneity in Sickle Cell Disease

Overview

Sickle cell disease (SCD) is characterized by chronic hemolytic anemia, painful crisis called vaso-occlusive crisis (VOC) and chronic inflammation. Activated platelets of SCD patients participated to both chronic inflammation and painful VOC. Platelets are anucleated cells from the fragmentation of megakaryocytes in bone marrow. The main aim of this study is to characterize the distribution of the different megakaryocyte subpopulations of sickle cell disease patients SS and SC and in particular the "immune" megakaryocytes CD148+CD48+ and to compare it with the platelet phenotype.

Platelets are activated in all sickle cell disease patients at baseline with higher expression of selective P (CD62P). Platelets provide a major function in primary hemostasis by the formation of the platelet clot and also participate in coagulation through the formation of an electro-negative phospholipid surface essential to the enzymes of the coagulation cascade. It is now known that platelets are also immune cells that are able to secrete pro-inflammatory cytokines (TGF beta, IFN gamma), that they express certain Toll-like receptors (TLR4) and the inflammasome NLRP3 leading to the activation of caspase-1. Several teams, including ours, have shown that inflammasome and/or caspase-1 can be activated in an infectious context, particularly viral (dengue fever, COVID) and inflammatory (chronic inflammatory bowel diseases, etc.). Platelets are anucleated cells from the fragmentation of megakaryocytes. Their protein profile is therefore the result of bone marrow differentiation of megakaryocytes. Recently, it has been shown a cellular heterogeneity within megakaryocytes including immune megakaryocytes whose proportion can significantly increase in stress and inflammation condition. It is not clear whether these immune megakaryocytes that could behave as antigen-presenting cells are capable of producing blood platelets. We wonder whether sickle cell disease patients have a different proportion of these immune megakaryocytes compared to healthy subjects and whether their activated blood platelets carry specific markers of these immune megakaryocytes. SCD patients will be recruited in the active file of the sickle cell center of Guadeloupe. Two groups of patients will be constituted: SS patients and SC patients. The control group will be composed of patients who come for hip or knee replacement and do not suffer from chronic disease. Only one blood and bone marrow collection will be realized during the study.