[Vasculopathy and inflammation in sickle cell anemia] : [i) study of the determinants of chronic vasculopathy in sub-Saharan Africa] : [ii) inflammatory dynamics of polynuclear neutrophils under transfusion therapy in a French cohort]

Abstract

Sickle cell disease is a severe genetic disease of the red blood cell caused by the substitution of glutamic acid by a valine at position 6 in the β-globin chain, resulting in the production of an abnormal hemoglobin (HbS). Its classic form is characterized by chronic anemia, acute vaso-occlusive events, the most characteristic being the painful vaso-occlusive crisis, and extreme susceptibility to infections. In France, it is the genetic disease with the highest incidence. Even though it is very common in sub-Saharan Africa (85% of the newborns with sickle cell disease), its natural history is poorly understood in this part of the world. It is now considered globally as a vascular disease, but the precise mechanisms of this vasculopathy as well as the associated risk factors are not clearly established. Studies carried out on series of patients in the United States have suggested the existence of two sub-phenotypes: the “hemolysis/endothelial dysfunction” sub-phenotype, on the one hand, and the “hyperviscosity/vaso-occlusion” sub-phenotype, on the other, each being associated with a specific group of complications. In the first part of our work, we sought to define the determinants of the sickle cell vasculopathy in sub-Saharan Africa. To this purpose, we carried out a case-control study on 232 homozygous SS adults followed for more than 5 years in Dakar (Senegal) and Bamako (Mali) in two of the five centers of the CADRE cohort, the largest African cohort established since 2011 (Cœur, Artère, DRépanocytose / Heart, Artery, Sickle Cell Disease, NCTO3114137). Patients were characterized according to the presence or absence of the following complications: tricuspid regurgitation velocity (TRV) > 2.5 m/s (associated with pulmonary hypertension), micro/macroalbuminuria, leg ulcer, priapism, osteonecrosis, and retinopathy. In these patients beyond the routine biological examinations, we analyzed the level and cellular distribution of circu