Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
MR and MDHD contributed equally to this work. Summary Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence , we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxi-dase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil-and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.
ISSN: 0007-1048

inserm-01476067
http://www.hal.inserm.fr/inserm-01476067
http://www.hal.inserm.fr/inserm-01476067/document
http://www.hal.inserm.fr/inserm-01476067/file/2016%2C%20Hierso%20-%20Exacerbation%20of%20oxidative%20stress%20during%20sickle%20vaso-occlusive%20crisis.pdf
DOI : 10.1111/bjh.14476

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
It is unclear whether vascular function is affected similarly in children with sickle cell anaemia (SS) and children with sickle haemoglobin C (SC) disease. Therefore, we compared micro and macrovascular functions in healthy (AA) children, children with SS and SC disease, and assessed their association with physical activity. Participants (24 SS, 22 SC and 16 AA), were compared in terms of 1) thermal hyperaemic response (finger pad warming to 42 °C) measured by Laser Doppler techniques, 2) arterial stiffness determined by pulse wave velocity, 3) daily energy expenditure related to moderate and intense physical activities estimated by questionnaire and 4) fitness level, evaluated by the six-minute walk test. Response to heating differed between SS, SC and controls. Peripheral microvascular reactivity was lower and pulse wave velocity higher in SS compared to AA. SC had blunted microvascular reactivity in response to heating compared to AA but pulse wave velocity was not different within the two groups. Physical activity and fitness levels were markedly lower in sickle cell patients compared to healthy controls but no association was observed with vascular function. Microvasodilatory reserve is decreased in both SS and SC patients but only SS patients were also characterised by impaired macrovascular function.
ISSN: 1079-9796

hal-01496857
https://hal.archives-ouvertes.fr/hal-01496857
https://hal.archives-ouvertes.fr/hal-01496857/document
https://hal.archives-ouvertes.fr/hal-01496857/file/Mo%CC%88ckesch%20et%20al%20BCMD%20non%20apparent%20corrections%20final.pdf
DOI : 10.1016/j.bcmd.2017.02.001

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Painful vaso-occlusive crisis, a hallmark of sickle cell anaemia, results from complex, incompletely understood mechanisms. Red blood cell (RBC) damage caused by continuous endogenous and exogenous oxidative stress may precipitate the occurrence of vaso-occlusive crises. In order to gain insight into the relevance of oxidative stress in vaso-occlusive crisis occurrence, we prospectively compared the expression levels of various oxidative markers in 32 adults with sickle cell anaemia during vaso-occlusive crisis and steady-state conditions. Compared to steady-state condition, plasma levels of free haem, advanced oxidation protein products and myeloperoxidase, RBC caspase-3 activity, as well as the concentrations of total, neutrophil- and RBC-derived microparticles were increased during vaso-occlusive crises, whereas the reduced glutathione content was decreased in RBCs. In addition, natural anti-band 3 autoantibodies levels decreased during crisis and were negatively correlated with the rise in plasma advanced oxidation protein products and RBC caspase-3 activity. These data showed an exacerbation of the oxidative stress during vaso-occlusive crises in sickle cell anaemia patients and strongly suggest that the higher concentration of harmful circulating RBC-derived microparticles and the reduced anti-band 3 autoantibodies levels may be both related to the recruitment of oxidized band 3 into membrane aggregates.
ISSN: 0007-1048

hal-01668325
https://hal.univ-antilles.fr/hal-01668325
DOI : 10.1111/bjh.14476

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Hydroxycarbamide (HC) treatment has been shown to improve the clinical course of patients with sickle cell anaemia (SCA), a haemoglobinopathy resulting from a single base substitution in the bêta-globin gene (HBB). SCA is characterized by chronic haemolytic anaemia and recurrent vascular occlusions leading to multisystemic complications. Several beneficial biological effects of HC have been documented (Halsey et al, 2003) but its impact on the concentration of circulating microparticles (MPs), a subtype of extracellular vesicles released from cytoplasmic membrane of activated or apoptotic cells and detected at high levels in sickle plasma, remains controversial (Hebbel et al, 2016). The aim of the present study was to compare the MP pattern in a group of SCA patients treated by HC and followed for 2 years.
ISSN: 0007-1048

hal-01668320
https://hal.univ-antilles.fr/hal-01668320
https://hal.univ-antilles.fr/hal-01668320/document
https://hal.univ-antilles.fr/hal-01668320/file/Garnier%20et%20al%20BJH-2017-00655.pdf
DOI : 10.1111/bjh.14810

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
OBJECTIVES:Blood rheology plays a key role in the pathophysiology of sickle cell anaemia (SS) and sickle cell haemoglobin C disease (SC), but its evolution over the lifespan is unknown.MATERIALS AND METHODS:Blood viscosity, red blood cell (RBC) deformability and aggregation, foetal haemoglobin (HbF) and haematocrit were measured in 114 healthy individuals (AA), 267 SS (161 children + 106 adults) and 138 SC (74 children + 64 adults) patients.RESULTS:Our results showed that 1) RBC deformability is at its maximal value during the early years of life in SS and SC populations, mainly because HbF level is also at its peak, 2) during childhood and adulthood, hydroxycarbamide treatment, HbF level and gender modulated RBC deformability in SS patients, independently of age, 3) blood viscosity is higher in older SS and SC patients compared to younger ones and 4) haematocrit decreases as SS patients age.CONCLUSION:The hemorheological changes detected in older patients could play a role in the progressive development of several chronic disorders in sickle cell disease, whose prevalence increases with age. Retarding these age-related haemorheological impairments, by using suitable drugs, may minimize the risks of vaso-occlusive events and chronic disorders.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01669747
https://hal.univ-antilles.fr/hal-01669747
DOI : 10.1371/journal.pone.0158182
PUBMED : 27355589
PUBMEDCENTRAL : PMC4927160

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Sickle cell anaemia (SCA) is the most frequent genetic haemoglobinopathy, which exhibits a highly variable clinical course characterized by hyper-coagulable and pro-inflammatory states, as well as endothelial dysfunction. Extracellular microvesicles are released into biological fluids and play a role in modifying the functional phenotype of target cells. We hypothesized that potential differences in plasma-derived extracellular microvesicles (EV) function and cargo from SCA patients may underlie divergent clinical trajectories. Plasma EV from SCA patients with mild, intermediate and severe clinical disease course were isolated, and primary endothelial cell cultures were exposed. Endothelial cell activation, monocyte adhesion, barrier disruption and exosome cargo (microRNA microarrays) were assessed. EV disrupted the endothelial barrier and induced expression of adhesion molecules and monocyte adhesion in a SCA severity-dependent manner compared to healthy children. Microarray approaches identified a restricted signature of exosomal microRNAs that readily distinguished severe from mild SCA, as well as from healthy children. The microRNA candidates were further validated using quantitative real time polymerase chain reaction assays, and revealed putative gene targets. Circulating exosomal microRNAs may play important roles in predicting the clinical course of SCA, and in delineation of individually tailored, mechanistically-based clinical treatment approaches of SCA patients in the near future.
ISSN: 0007-1048

hal-01668328
https://hal.univ-antilles.fr/hal-01668328
DOI : 10.1111/bjh.14104

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
Oxidative stress and haemolysis-associated nitric oxide (NO) depletion plays a crucial role in the development of vasculopathy in sickle cell anaemia (SS). However it remains unknown whether oxidative stress and haemolysis levels influence vascular function in patients with sickle haemoglobin C disease (SC). Microvascular response to heat (using Laser Doppler flowmetry on finger), oxidative stress biomarkers, NO metabolites, endothelin-1 and haematological parameters were compared between patients with SS and SC. Vascular function, oxidative and nitrosative markers were also measured in healthy (AA) children. SS and SC had increased plasma advanced oxidation protein products (AOPP), malondialdehyde, plasma antioxidant activities and NO end products, compared to AA. SC had lower catalase activity compared to AA and SS. Haemolytic rate, glutathione peroxidase and nitrotyrosine concentrations were significantly increased in children with SS compared to SC and AA. SS and SC had impaired microvascular reactivity compared to AA. In SS, the plateau phase of the response to local thermal heating was negatively associated with nitrotyrosine and AOPP. No association between vascular function parameters and oxidative stress markers was observed in SC. Mild haemolysis in SC, compared to SS, may limit oxidative and nitrosative stress and could explain the better preserved microvascular function in this group.
ISSN: 0007-1048

hal-01668314
https://hal.univ-antilles.fr/hal-01668314
DOI : 10.1111/bjh.14693

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND:Sickle cell anaemia (SCA) is a severe hereditary haemoglobinopathy characterised by haemorheological abnormalities, which play a role in the occurrence of several acute and chronic clinical complications. While βS -haplotypes and alpha-thalassaemia modulate SCA clinical severity, their effects on blood rheology have been incompletely described. The aim of this study was to test the effects of these genetic modifiers on the haemorheological properties and clinical complication of children with SCA.PROCEDURE:Steady-state haemorheological profile, biological parameters, βS -haplotypes, alpha-globin status, vaso-occlusive crisis (VOC) and acute chest syndrome frequencies were analysed in 128 children (aged 5 to 18 years) with SCA.RESULTS:Patients with alpha-thalassaemia showed increased red blood cell (RBC) deformability and aggregation compared to those without. Median VOC rate was higher in patients with homozygous alpha-thalassaemia compared to those with a normal alpha genotype. Conversely, the haemorheological profile and clinical complications were not influenced by the βS -haplotypes in our study.CONCLUSION:Our results demonstrate that alpha-thalassaemia is associated with higher risk for VOC events in children with SCA, which may be due in part to its effects on RBC deformability and aggregation.
ISSN: 1545-5009

hal-01668317
https://hal.univ-antilles.fr/hal-01668317
DOI : 10.1002/pbc.26455
PUBMED : 28097791