Yves Colin - Academia.edu (original) (raw)

Papers by Yves Colin

Research paper thumbnail of RhBG and RhCG, the Putative Ammonia Transporters, Are Expressed in the Same Cells in the Distal Nephron

Journal of The American Society of Nephrology, Mar 1, 2003

Two nonerythroid homologs of the blood group Rh proteins, RhCG and RhBG, which share homologies w... more Two nonerythroid homologs of the blood group Rh proteins, RhCG and RhBG, which share homologies with specific ammonia transporters in primitive organisms and plants, could represent members of a new family of proteins involved in ammonia transport in the mammalian kidney. Consistent with this hypothesis, the expression of RhCG was recently reported at the apical pole of all connecting tubule (CNT) cells as well as in intercalated cells of collecting duct (CD). To assess the localization along the nephron of RhBG, polyclonal antibodies against the Rh type B glycoprotein were generated. In immunoblot experiments, a specific polypeptide of Mr approximately 50 kD was detected in rat kidney cortex and in outer and inner medulla membrane fractions. Immunocytochemical studies revealed RhBG expression in distal nephron segments within the cortical labyrinth, medullary rays, and outer and inner medulla. RhBG expression was restricted to the basolateral membrane of epithelial cells. The same localization was observed in rat and mouse kidney. RT-PCR analysis on microdissected rat nephron segments confirmed that RhBG mRNAs were chiefly expressed in CNT and cortical and outer medullary CD. Double immunostaining with RhCG demonstrated that RhBG and RhCG were coexpressed in the same cells, but with a basolateral and apical localization, respectively. In conclusion, RhBG and RhCG are present in a major site of ammonia secretion in the kidney, i.e., the CNT and CD, in agreement with their putative role in ammonium transport.

Research paper thumbnail of Rapid Cl<sup>−</sup>/HCO<sub>3</sub><sup>−</sup>exchange kinetics of AE1 in HEK293 cells and hereditary stomatocytosis red blood cells

American Journal of Physiology-cell Physiology, Sep 15, 2013

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Research paper thumbnail of Relevance of Howell‐Jolly body counts for measuring spleen function in sickle cell disease

American Journal of Hematology

Research paper thumbnail of Platelet caspase‐1 and Bruton tyrosine kinase activation in patients with COVID‐19 is associated with disease severity and reversed in vitro by ibrutinib

Research and Practice in Thrombosis and Haemostasis

Research paper thumbnail of Genetic Evidence That Dimerization of Glycophorin a Is Critical for Red Cell Invasion By Plasmodium Falciparum but Not for the Binding of EBA-175

Research paper thumbnail of The First Two Years of Life in Sickle Cell Anemia Infants: Results of a Comprehensive Longitudinal Study

Blood, 2017

Background and hypothesis: Infancy is a critical time during which the first complications of sic... more Background and hypothesis: Infancy is a critical time during which the first complications of sickle cell anemia (SCA) emerge. Very early prognostic factors of severity are needed to select high-risk children to offer precisely tailored therapy. Our hypothesis was that clinical, biological or genetic parameters measurable soon after birth (3 to 6 months of age) could predict severe outcomes in the first two years of life in SCA infants. Methods: Infants with SCA were offered to participate in a prospective study (ClinicalTrials.gov: NCT01207037) that included clinical and laboratory assessment at enrollment (3-6 months) and at 12, 18 and 24 months of age. The prognostic performance of conventional and SCA-specific biomarkers (notably erythroid adhesion markers, dense cells, ektacytometry indices) on disease severity was assessed using Cox's proportional hazard regression models. The disease severity was defined as time to first occurrence of either acute splenic sequestration (A...

Research paper thumbnail of New Insights into F-Cells, F-Reticulocytes and the Role of Fetal Hemoglobin in Protecting Sickle Red Cells from Hemolysis upon Mechanical Stress

Research paper thumbnail of Revisiting Spleen Function and Pneumococcal Risk in Children with Hemoglobin SC Disease

Blood, 2021

Spleen dysfunction and susceptibility to pneumococcal infection is a well known feature in homozy... more Spleen dysfunction and susceptibility to pneumococcal infection is a well known feature in homozygous sickle cell disease (HbSS), whilst to date splenic function in hemoglobin SC disease (HbSC) has been poorly investigated. The aim of this study was to analyze spleen function in children with HbSC disease using a high-throughput validated method (1) and to examine if the current recommendations regarding pneumococcal risk are appropriate in this population. Spleen function was evaluated using a flow cytometry quantification of red blood cells (RBCs) with Howell-Jolly bodies (HJBs), in a cross-sectional study of patients at steady state during an outpatient visit in an expert center. Quantification of HJB-RBCs was performed in children with HbSC disease aged < 10 years and compared to children with HbSS disease or healthy children of the same age groups, or splenectomized children. Additional exploratory analysis was performed according to age (under or above the age of 5 years ol...

Research paper thumbnail of Relationship between chimpanzee Rh‐like genes and the R‐C‐E‐F blood group system

Journal of Medical Primatology, 1993

The antigenic closeness between the chimpanzee alloantigen Rc of the R‐C‐E‐F system, and the huma... more The antigenic closeness between the chimpanzee alloantigen Rc of the R‐C‐E‐F system, and the human alloantigen Rho(D) suggests a phylogeconnection between their genes. To confirm at the molecular level the common origin of these genes, genomic DNA from 16 unrelated chimpanzees of various R‐C‐E‐F phenotypes were digested by three restriction enzymes and analyzed by Southern blot using a human Rh cDNA probe and three exon‐specific probes. Restrictions profiles displayed reach polymorphism. Correlations between some bands and certain R‐C‐E‐F phenotypes demonstrate that the human Rh cDNA probe defines in chimpanzee genomic DNA some genes of the R‐C‐E‐F system.

Research paper thumbnail of Adenosine Signaling Perturbs Erythropoiesis and Promotes Myeloid Differentiation

Blood, 2021

Background Adenosine is a major signaling nucleoside that activates cellular signaling pathways t... more Background Adenosine is a major signaling nucleoside that activates cellular signaling pathways through a family of four different G protein-coupled adenosine receptors (ARs), A 1, A 2A, A 2B, and A 3. At steady state conditions, extracellular levels of adenosine remain low (10 to 200 nM) either through its rapid cellular uptake by specialized nucleoside transporters, mainly through the equilibrative nucleoside transporter 1 (ENT1), or its degradation by adenosine deaminases. However, the extracellular levels of adenosine can be rapidly elevated up to 100 μM in response to hypoxia, inflammation, or tissue injury. Under pathophysiological conditions, adenosine signaling is involved in modulating inflammation, fibrosis, and ischemic tissue injury. In sickle cell disease (SCD), adenosine signaling is enhanced and contributes to the pathophysiology of the disease. Despite the importance of adenosine signaling in regulating cell proliferation, and stem cell regeneration, as well as in re...

Research paper thumbnail of Persistance of Inflammatory Phenotype of Neutrophils in Sickle Cell Disease Children Despite Chronic Exchange Transfusion Program: A Cause of the Progression of Cerebral Vasculopathy?

Blood, 2020

Sickle cell disease (SCD) is a severe hemoglobinopathy due to the production of abnormal hemoglob... more Sickle cell disease (SCD) is a severe hemoglobinopathy due to the production of abnormal hemoglobin S (HbS). Although red blood cell (RBC) dysfunction is the major contributor to disease, several studies highlighted the important role of polymorphonuclear neutrophils (PMNs), both during acute and chronic complications. One of the most severe complication of SCD is ischemic stroke due to large cerebral artery occlusion. In 1998, the Stroke Prevention (STOP) trial demonstrated that monthly blood transfusions could reduce the risk of stroke by 90% in SCD children with cerebral vasculopathy (CV). However, there is a wide heterogeneity in the course of CV in patients receiving chronic transfusions, since only about half of them improved their CV under transfusion program, while 25% are only stabilized and 29% continue to get worse despite a percentage of HbS permanently below 30%. The aim of our study is to investigate the impact of transfusion programs on neutrophils activation and agei...

Research paper thumbnail of Cell‐derived microparticles and sickle cell disease chronic vasculopathy in sub‐Saharan Africa: A multinational study

British Journal of Haematology, 2020

Long-term eddy covariance measurements of energy and water fluxes and associated climatic paramet... more Long-term eddy covariance measurements of energy and water fluxes and associated climatic parameters were carried out above a Scots pine (Pinus sylvestris) forest in the middle taiga zone of Central Siberia. Data from June 1998 through October 2000 are presented. With the exception of winter 1998/1999, data collection over this period were more or less continuous. A distinct seasonality in surface energy exchange characteristics was observed in all years. In early spring in the absence of physiological activity by the vegetation, about 80% of the net radiation was partitioned for sensible heat, resulting in Bowen ratios, β, as high as 8. In the 1-2 wk period associated with onset of photosynthesis in spring, evaporation rates increased rapidly and β rapidly dropped. However, even during summer months, sensible heat fluxes typically exceeded latent heat fluxes and β remained above 2.0. Observed daily evaporation rates varied between 0.5-1.0 mm d -1 in spring and autumn and 1.5-2 mm d -1 in midsummer. The overall average for the three growing seasons examined was 1.25 mm d -1 . Precipitation was on average 230 mm for the growing period, with evaporation over the same time being about 190 mm for both 1999 and 2000. This represented only about 35% of the equilibrium evaporation rate. There was typically a positive hydrological balance of 40 mm for the growing season as a whole. However, in all three years examined, evaporation exceeded precipitation totals by 20-40 mm in at least one calendar month during summer. During the growing season, daily averaged surface conductances varied between 0.15 and 0.20 mol m -2 s -1 (3-4.5 mm s -1 ) in dry or cool months and 0.30-0.35 mol m -2 s -1 (6.5-8 mm s -1 ) in moist and warm months. Despite a negative hydrological balance during midsummer, there was little evidence for reduced canopy conductances in response to soil water deficits. This may have been the consequence of roots accessing water from within or just above a perched water table, located at about 2 m depth.

Research paper thumbnail of Storage-Induced Micro-Erythrocytes Are Rapidly Cleared from Recipient Circulation and Predict Transfusion Recovery

Blood, 2019

Background Hypothermic storage of red blood cell (RBC) concentrates for up to 42 days is associat... more Background Hypothermic storage of red blood cell (RBC) concentrates for up to 42 days is associated with biochemical, molecular, morphological, and mechanical modifications. This "storage lesion" increases with storage duration and is associated with increased clearance of transfused storage-damaged RBCs from the recipient's circulation in the first few hours post-transfusion. This rapid clearance reduces transfusion efficacy, but how it occurs is not fully elucidated. RBCs with reduced surface area called "storage-induced micro-erythrocytes" (SMEs) were recently described. Their proportion increases from 2% to 23% during storage. Their reduced surface-to-volume ratio is expected to induce rapid mechanical clearance by the spleen. We aimed to evaluate whether SMEs can be used as a marker of transfusion efficacy, if this subpopulation of RBCs is preferentially cleared by the spleen after transfusion, and if so, by which mechanisms. Methods We evaluated the pro...

Research paper thumbnail of Variation of Red Blood Cell Rheology and Adhesiveness during Vaso-Occlusive Crises in Sickle Cell Patients

Blood, 2016

Introduction: Impaired red blood cell (RBC) rheology, increased RBC adhesiveness to the vascular ... more Introduction: Impaired red blood cell (RBC) rheology, increased RBC adhesiveness to the vascular wall, enhanced inflammation and blunted vascular reactivity are involved in the pathophysiology of sickle cell anemia (SCA). Painful vaso-occlusive crisis (VOC) is the most frequent complication encountered by SCA patients. While several studies compared several biomarkers of severity between patients at steady state and others during VOC, very few works compared the same patients in the two conditions. It is therefore difficult to know what happens during VOC. The present study was devoted to compare several hematological, biochemical, and rheological parameters, as well as RBC adhesiveness at steady state and during VOC. Altogether, 36 SCA patients were studied. Methods: This prospective monocentric study was performed at the University Hospital of Pointe-a-Pitre (Guadeloupe, French West Indies), in accordance with the guidelines set by the declaration of Helsinki and was approved by t...

Research paper thumbnail of Studying the Determinant of Sickle Cell Disease Vasculopathy in Sub-Saharan Africa : The Biocadre Study

Blood, 2019

Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the history ... more Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the history of the disease in this continent remains largely unknown. SCD is characterized by chronic hemolytic anemia, acute-vaso occlusive events and progressive vascular organ damage. The CADRE study is a large cohort of SCD patients in five countries of West and Central Africa aiming at studying SCD-related vascular complications. The inclusion data of this study did not match the hyper-hemolysis paradigm (Dubert et al. Blood 2018), but several methodological limitations were raised, including probable mortality bias and questionable reliability of classical hemolysis markers in Africa. For the 5-year follow-up of the CADRE study, we designed a case-control study nested in the cohort, based on extreme phenotypes, to look for new markers of vasculopathy, including new markers of hemolysis. Patients and Methods SS adult patients of the CADRE cohort were selected in the centres of Dakar (Senegal) a...

Research paper thumbnail of CELL-Derived Microparticles and Sickle CELL Disease Chronic Vasculopathy in Sub-Saharan Africa

Blood, 2019

Introduction Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa,... more Introduction Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the history of the disease on this continent remains largely unknown. SCD is characterized by the association of chronic hemolytic anemia with episodes of acute vaso-occlusive events and progressive vascular organ damage. Several pathophysiological pathways in SCD result in the activation of circulating blood cells and the release of microparticles (MPs). In the present study, we investigated cell-derived MPs in patients with SCD living in Africa and analyzed their relationship with clinical complications. Patients and Methods This cross-sectional case-control study is nested in the CADRE cohort (clinical trials.gov identifier NCTO3114137). We included 232 SS adults in two African centers: Bamako (Mali) and Dakar (Senegal). Patients were chosen depending on the absence or the presence of at least one of the following complications: tricuspid regurgitant jet velocity (TRJV) >3 m/s (wh...

Research paper thumbnail of Effects of Poloxamer 188 on Red Blood Cells Membrane Properties in Sickle Cell Disease

Blood, 2015

Introduction: Sickle cell anemia (SCA) is a severe monogenic hereditary disorder characterized by... more Introduction: Sickle cell anemia (SCA) is a severe monogenic hereditary disorder characterized by chronic hemolytic anemia and the occurrence of frequent painful vaso-occlusive crises (VOC). SCA classical physiological scheme involves hemoglobin S polymerization under hypoxic conditions, which triggers red blood cells (RBCs) sickling. Recent studies demonstrated that the degree of hemorheological alterations, such as blood hyper-viscosity, determines the risk for VOC. Moreover, sickle RBCs abnormally adhere to the vascular endothelium, triggering microvascular occlusions. Despite extensive research very few drugs are available to efficiently treat VOCs or VOC-like events. A first clinical trial was performed to test the efficacy of poloxamer 188 (P188) in a large sickle cell cohort of adults and children (Orringer et al., 2001). This study demonstrated a significant reduction of pain duration in the children treated with P188. Recently, a new phase III multi-center trial has been st...

Research paper thumbnail of The Endothelin Receptor Etb Plays a Crucial Role for Recruitment of Neutrophils to the Vascular Wall in Sickle Cell Disease

Blood, 2016

Introduction: Although Sickle Cell Disease (SCD) is due to abnormal hemoglobin, many cell types, ... more Introduction: Although Sickle Cell Disease (SCD) is due to abnormal hemoglobin, many cell types, including endothelial cells and polymorphonuclear neutrophils (PMNs), play a key role in the pathophysiology of the disease, particularly in the vaso-occlusive events. Adhesion of PMNs to activated endothelium is critical in SCD and might contribute to vaso-occlusion; thus targeting PMN interactions with the endothelium may represent a good opportunity for new therapeutics. We looked for candidate mediators that may be involved in PMN activation and recruitment in tissues. We focused on endothelin-1 (ET-1) since (i) high levels of cytokines have been reported in SCD patients; (ii) we previously demonstrated that ET-1 receptors blockade in the SAD mouse model of SCD leads to reversal or prevention of vaso-occlusive events, nitrative stress, kidney and lung damage, and even death. While demonstrating that ET receptor (ETR) antagonism inhibited a tonic ET-1-dependent vasoconstriction during...

Research paper thumbnail of Rh blood group antigens: from antenatal diagnosis of haemolytic disease of the new born to ammonium transport function

Hematologie, Sep 1, 2004

Le systeme RH (rhesus) est un des systemes de groupe sanguin les plus immunogenes et les plus pol... more Le systeme RH (rhesus) est un des systemes de groupe sanguin les plus immunogenes et les plus polymorphes chez l’homme. Les bases moleculaires de la grande majorite des phenotypes Rh, y compris le phenotype Rh null associe a une anemie hemolytique de severite variable, sont aujourd’hui elucidees. En particulier, la demonstration que le locus RH des individus RhD-positifs est compose des genes RHD et RHCE alors que celui des individus RhD-negatifs ne possede, tout du moins dans la population caucasienne, que le gene RHCE, a permis le developpement d’un diagnostic antenatal des grossesses a risque de maladie hemolytique du nouveau-ne par des tests PCR invasifs (ADN de cellules amniotiques) et non invasifs (ADN fœtal circulant dans le plasma maternel). Les antigenes Rh sont presents dans la membrane du globule rouge au sein du « complexe Rh » forme de l’association des proteines Rh (D et/ou CE), RhAG (Rh associated glycoprotein), LW (ICAM-4), CD47 (IAP) et glycophorine B (GPB). Le complexe Rh serait lui-meme associe a l’echangeur d’anions AE1 (Bande 3). Grâce a ses interactions avec les proteines adaptatrices 4.2 et ankyrine, il contribue a la stabilite et au maintien des proprietes mecaniques de la membrane erythrocytaire. Ainsi, les deficits primaires en proteines Rh ou RhAG, ankyrine ou proteine 4.2 sont tous associes a des spherocytoses hereditaires, typiques ou atypiques. Au-dela de ses deux membres erythroides, Rh et RhAG, la famille des proteines Rh comprend chez les mamiferes deux membres non erythroides, RhBG et RhCG, exprimes essentiellement dans des organes impliques dans la production et l’excretion d’ammonium comme le foie et le rein. Des analyses fonctionnelles dans des systemes d’expression heterologues ou dans des globules rouges de variants naturels ont permis de demontrer que les proteines RhAG, RhBG et RhCG peuvent fonctionner comme des transporteurs d’ammonium (NH 3 et/ou NH 4 +). Ces transporteurs specifiques d’ammonium, les premiers identifies a ce jour chez les mammiferes, pourraient ainsi participer a l’elimination de la charge acide quotidienne generee par le metabolisme. L’ensemble de ces resultats designe les proteines Rh comme de nouveaux elements cles de la structure et de la fonction de la membrane des cellules erythroides et epitheliales.

Research paper thumbnail of Les antigènes de groupe sanguin Rh : du diagnostic anténatal de la maladie hémolytique du nouveau-né à la fonction de transport d’ammonium

Hematologie, Sep 1, 2004

Le systeme RH (rhesus) est un des systemes de groupe sanguin les plus immunogenes et les plus pol... more Le systeme RH (rhesus) est un des systemes de groupe sanguin les plus immunogenes et les plus polymorphes chez l’homme. Les bases moleculaires de la grande majorite des phenotypes Rh, y compris le phenotype Rh null associe a une anemie hemolytique de severite variable, sont aujourd’hui elucidees. En particulier, la demonstration que le locus RH des individus RhD-positifs est compose des genes RHD et RHCE alors que celui des individus RhD-negatifs ne possede, tout du moins dans la population caucasienne, que le gene RHCE, a permis le developpement d’un diagnostic antenatal des grossesses a risque de maladie hemolytique du nouveau-ne par des tests PCR invasifs (ADN de cellules amniotiques) et non invasifs (ADN fœtal circulant dans le plasma maternel). Les antigenes Rh sont presents dans la membrane du globule rouge au sein du « complexe Rh » forme de l’association des proteines Rh (D et/ou CE), RhAG (Rh associated glycoprotein), LW (ICAM-4), CD47 (IAP) et glycophorine B (GPB). Le complexe Rh serait lui-meme associe a l’echangeur d’anions AE1 (Bande 3). Grâce a ses interactions avec les proteines adaptatrices 4.2 et ankyrine, il contribue a la stabilite et au maintien des proprietes mecaniques de la membrane erythrocytaire. Ainsi, les deficits primaires en proteines Rh ou RhAG, ankyrine ou proteine 4.2 sont tous associes a des spherocytoses hereditaires, typiques ou atypiques. Au-dela de ses deux membres erythroides, Rh et RhAG, la famille des proteines Rh comprend chez les mamiferes deux membres non erythroides, RhBG et RhCG, exprimes essentiellement dans des organes impliques dans la production et l’excretion d’ammonium comme le foie et le rein. Des analyses fonctionnelles dans des systemes d’expression heterologues ou dans des globules rouges de variants naturels ont permis de demontrer que les proteines RhAG, RhBG et RhCG peuvent fonctionner comme des transporteurs d’ammonium (NH 3 et/ou NH 4 +). Ces transporteurs specifiques d’ammonium, les premiers identifies a ce jour chez les mammiferes, pourraient ainsi participer a l’elimination de la charge acide quotidienne generee par le metabolisme. L’ensemble de ces resultats designe les proteines Rh comme de nouveaux elements cles de la structure et de la fonction de la membrane des cellules erythroides et epitheliales.

Research paper thumbnail of RhBG and RhCG, the Putative Ammonia Transporters, Are Expressed in the Same Cells in the Distal Nephron

Journal of The American Society of Nephrology, Mar 1, 2003

Two nonerythroid homologs of the blood group Rh proteins, RhCG and RhBG, which share homologies w... more Two nonerythroid homologs of the blood group Rh proteins, RhCG and RhBG, which share homologies with specific ammonia transporters in primitive organisms and plants, could represent members of a new family of proteins involved in ammonia transport in the mammalian kidney. Consistent with this hypothesis, the expression of RhCG was recently reported at the apical pole of all connecting tubule (CNT) cells as well as in intercalated cells of collecting duct (CD). To assess the localization along the nephron of RhBG, polyclonal antibodies against the Rh type B glycoprotein were generated. In immunoblot experiments, a specific polypeptide of Mr approximately 50 kD was detected in rat kidney cortex and in outer and inner medulla membrane fractions. Immunocytochemical studies revealed RhBG expression in distal nephron segments within the cortical labyrinth, medullary rays, and outer and inner medulla. RhBG expression was restricted to the basolateral membrane of epithelial cells. The same localization was observed in rat and mouse kidney. RT-PCR analysis on microdissected rat nephron segments confirmed that RhBG mRNAs were chiefly expressed in CNT and cortical and outer medullary CD. Double immunostaining with RhCG demonstrated that RhBG and RhCG were coexpressed in the same cells, but with a basolateral and apical localization, respectively. In conclusion, RhBG and RhCG are present in a major site of ammonia secretion in the kidney, i.e., the CNT and CD, in agreement with their putative role in ammonium transport.

Research paper thumbnail of Rapid Cl<sup>−</sup>/HCO<sub>3</sub><sup>−</sup>exchange kinetics of AE1 in HEK293 cells and hereditary stomatocytosis red blood cells

American Journal of Physiology-cell Physiology, Sep 15, 2013

HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific r... more HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Research paper thumbnail of Relevance of Howell‐Jolly body counts for measuring spleen function in sickle cell disease

American Journal of Hematology

Research paper thumbnail of Platelet caspase‐1 and Bruton tyrosine kinase activation in patients with COVID‐19 is associated with disease severity and reversed in vitro by ibrutinib

Research and Practice in Thrombosis and Haemostasis

Research paper thumbnail of Genetic Evidence That Dimerization of Glycophorin a Is Critical for Red Cell Invasion By Plasmodium Falciparum but Not for the Binding of EBA-175

Research paper thumbnail of The First Two Years of Life in Sickle Cell Anemia Infants: Results of a Comprehensive Longitudinal Study

Blood, 2017

Background and hypothesis: Infancy is a critical time during which the first complications of sic... more Background and hypothesis: Infancy is a critical time during which the first complications of sickle cell anemia (SCA) emerge. Very early prognostic factors of severity are needed to select high-risk children to offer precisely tailored therapy. Our hypothesis was that clinical, biological or genetic parameters measurable soon after birth (3 to 6 months of age) could predict severe outcomes in the first two years of life in SCA infants. Methods: Infants with SCA were offered to participate in a prospective study (ClinicalTrials.gov: NCT01207037) that included clinical and laboratory assessment at enrollment (3-6 months) and at 12, 18 and 24 months of age. The prognostic performance of conventional and SCA-specific biomarkers (notably erythroid adhesion markers, dense cells, ektacytometry indices) on disease severity was assessed using Cox's proportional hazard regression models. The disease severity was defined as time to first occurrence of either acute splenic sequestration (A...

Research paper thumbnail of New Insights into F-Cells, F-Reticulocytes and the Role of Fetal Hemoglobin in Protecting Sickle Red Cells from Hemolysis upon Mechanical Stress

Research paper thumbnail of Revisiting Spleen Function and Pneumococcal Risk in Children with Hemoglobin SC Disease

Blood, 2021

Spleen dysfunction and susceptibility to pneumococcal infection is a well known feature in homozy... more Spleen dysfunction and susceptibility to pneumococcal infection is a well known feature in homozygous sickle cell disease (HbSS), whilst to date splenic function in hemoglobin SC disease (HbSC) has been poorly investigated. The aim of this study was to analyze spleen function in children with HbSC disease using a high-throughput validated method (1) and to examine if the current recommendations regarding pneumococcal risk are appropriate in this population. Spleen function was evaluated using a flow cytometry quantification of red blood cells (RBCs) with Howell-Jolly bodies (HJBs), in a cross-sectional study of patients at steady state during an outpatient visit in an expert center. Quantification of HJB-RBCs was performed in children with HbSC disease aged < 10 years and compared to children with HbSS disease or healthy children of the same age groups, or splenectomized children. Additional exploratory analysis was performed according to age (under or above the age of 5 years ol...

Research paper thumbnail of Relationship between chimpanzee Rh‐like genes and the R‐C‐E‐F blood group system

Journal of Medical Primatology, 1993

The antigenic closeness between the chimpanzee alloantigen Rc of the R‐C‐E‐F system, and the huma... more The antigenic closeness between the chimpanzee alloantigen Rc of the R‐C‐E‐F system, and the human alloantigen Rho(D) suggests a phylogeconnection between their genes. To confirm at the molecular level the common origin of these genes, genomic DNA from 16 unrelated chimpanzees of various R‐C‐E‐F phenotypes were digested by three restriction enzymes and analyzed by Southern blot using a human Rh cDNA probe and three exon‐specific probes. Restrictions profiles displayed reach polymorphism. Correlations between some bands and certain R‐C‐E‐F phenotypes demonstrate that the human Rh cDNA probe defines in chimpanzee genomic DNA some genes of the R‐C‐E‐F system.

Research paper thumbnail of Adenosine Signaling Perturbs Erythropoiesis and Promotes Myeloid Differentiation

Blood, 2021

Background Adenosine is a major signaling nucleoside that activates cellular signaling pathways t... more Background Adenosine is a major signaling nucleoside that activates cellular signaling pathways through a family of four different G protein-coupled adenosine receptors (ARs), A 1, A 2A, A 2B, and A 3. At steady state conditions, extracellular levels of adenosine remain low (10 to 200 nM) either through its rapid cellular uptake by specialized nucleoside transporters, mainly through the equilibrative nucleoside transporter 1 (ENT1), or its degradation by adenosine deaminases. However, the extracellular levels of adenosine can be rapidly elevated up to 100 μM in response to hypoxia, inflammation, or tissue injury. Under pathophysiological conditions, adenosine signaling is involved in modulating inflammation, fibrosis, and ischemic tissue injury. In sickle cell disease (SCD), adenosine signaling is enhanced and contributes to the pathophysiology of the disease. Despite the importance of adenosine signaling in regulating cell proliferation, and stem cell regeneration, as well as in re...

Research paper thumbnail of Persistance of Inflammatory Phenotype of Neutrophils in Sickle Cell Disease Children Despite Chronic Exchange Transfusion Program: A Cause of the Progression of Cerebral Vasculopathy?

Blood, 2020

Sickle cell disease (SCD) is a severe hemoglobinopathy due to the production of abnormal hemoglob... more Sickle cell disease (SCD) is a severe hemoglobinopathy due to the production of abnormal hemoglobin S (HbS). Although red blood cell (RBC) dysfunction is the major contributor to disease, several studies highlighted the important role of polymorphonuclear neutrophils (PMNs), both during acute and chronic complications. One of the most severe complication of SCD is ischemic stroke due to large cerebral artery occlusion. In 1998, the Stroke Prevention (STOP) trial demonstrated that monthly blood transfusions could reduce the risk of stroke by 90% in SCD children with cerebral vasculopathy (CV). However, there is a wide heterogeneity in the course of CV in patients receiving chronic transfusions, since only about half of them improved their CV under transfusion program, while 25% are only stabilized and 29% continue to get worse despite a percentage of HbS permanently below 30%. The aim of our study is to investigate the impact of transfusion programs on neutrophils activation and agei...

Research paper thumbnail of Cell‐derived microparticles and sickle cell disease chronic vasculopathy in sub‐Saharan Africa: A multinational study

British Journal of Haematology, 2020

Long-term eddy covariance measurements of energy and water fluxes and associated climatic paramet... more Long-term eddy covariance measurements of energy and water fluxes and associated climatic parameters were carried out above a Scots pine (Pinus sylvestris) forest in the middle taiga zone of Central Siberia. Data from June 1998 through October 2000 are presented. With the exception of winter 1998/1999, data collection over this period were more or less continuous. A distinct seasonality in surface energy exchange characteristics was observed in all years. In early spring in the absence of physiological activity by the vegetation, about 80% of the net radiation was partitioned for sensible heat, resulting in Bowen ratios, β, as high as 8. In the 1-2 wk period associated with onset of photosynthesis in spring, evaporation rates increased rapidly and β rapidly dropped. However, even during summer months, sensible heat fluxes typically exceeded latent heat fluxes and β remained above 2.0. Observed daily evaporation rates varied between 0.5-1.0 mm d -1 in spring and autumn and 1.5-2 mm d -1 in midsummer. The overall average for the three growing seasons examined was 1.25 mm d -1 . Precipitation was on average 230 mm for the growing period, with evaporation over the same time being about 190 mm for both 1999 and 2000. This represented only about 35% of the equilibrium evaporation rate. There was typically a positive hydrological balance of 40 mm for the growing season as a whole. However, in all three years examined, evaporation exceeded precipitation totals by 20-40 mm in at least one calendar month during summer. During the growing season, daily averaged surface conductances varied between 0.15 and 0.20 mol m -2 s -1 (3-4.5 mm s -1 ) in dry or cool months and 0.30-0.35 mol m -2 s -1 (6.5-8 mm s -1 ) in moist and warm months. Despite a negative hydrological balance during midsummer, there was little evidence for reduced canopy conductances in response to soil water deficits. This may have been the consequence of roots accessing water from within or just above a perched water table, located at about 2 m depth.

Research paper thumbnail of Storage-Induced Micro-Erythrocytes Are Rapidly Cleared from Recipient Circulation and Predict Transfusion Recovery

Blood, 2019

Background Hypothermic storage of red blood cell (RBC) concentrates for up to 42 days is associat... more Background Hypothermic storage of red blood cell (RBC) concentrates for up to 42 days is associated with biochemical, molecular, morphological, and mechanical modifications. This "storage lesion" increases with storage duration and is associated with increased clearance of transfused storage-damaged RBCs from the recipient's circulation in the first few hours post-transfusion. This rapid clearance reduces transfusion efficacy, but how it occurs is not fully elucidated. RBCs with reduced surface area called "storage-induced micro-erythrocytes" (SMEs) were recently described. Their proportion increases from 2% to 23% during storage. Their reduced surface-to-volume ratio is expected to induce rapid mechanical clearance by the spleen. We aimed to evaluate whether SMEs can be used as a marker of transfusion efficacy, if this subpopulation of RBCs is preferentially cleared by the spleen after transfusion, and if so, by which mechanisms. Methods We evaluated the pro...

Research paper thumbnail of Variation of Red Blood Cell Rheology and Adhesiveness during Vaso-Occlusive Crises in Sickle Cell Patients

Blood, 2016

Introduction: Impaired red blood cell (RBC) rheology, increased RBC adhesiveness to the vascular ... more Introduction: Impaired red blood cell (RBC) rheology, increased RBC adhesiveness to the vascular wall, enhanced inflammation and blunted vascular reactivity are involved in the pathophysiology of sickle cell anemia (SCA). Painful vaso-occlusive crisis (VOC) is the most frequent complication encountered by SCA patients. While several studies compared several biomarkers of severity between patients at steady state and others during VOC, very few works compared the same patients in the two conditions. It is therefore difficult to know what happens during VOC. The present study was devoted to compare several hematological, biochemical, and rheological parameters, as well as RBC adhesiveness at steady state and during VOC. Altogether, 36 SCA patients were studied. Methods: This prospective monocentric study was performed at the University Hospital of Pointe-a-Pitre (Guadeloupe, French West Indies), in accordance with the guidelines set by the declaration of Helsinki and was approved by t...

Research paper thumbnail of Studying the Determinant of Sickle Cell Disease Vasculopathy in Sub-Saharan Africa : The Biocadre Study

Blood, 2019

Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the history ... more Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the history of the disease in this continent remains largely unknown. SCD is characterized by chronic hemolytic anemia, acute-vaso occlusive events and progressive vascular organ damage. The CADRE study is a large cohort of SCD patients in five countries of West and Central Africa aiming at studying SCD-related vascular complications. The inclusion data of this study did not match the hyper-hemolysis paradigm (Dubert et al. Blood 2018), but several methodological limitations were raised, including probable mortality bias and questionable reliability of classical hemolysis markers in Africa. For the 5-year follow-up of the CADRE study, we designed a case-control study nested in the cohort, based on extreme phenotypes, to look for new markers of vasculopathy, including new markers of hemolysis. Patients and Methods SS adult patients of the CADRE cohort were selected in the centres of Dakar (Senegal) a...

Research paper thumbnail of CELL-Derived Microparticles and Sickle CELL Disease Chronic Vasculopathy in Sub-Saharan Africa

Blood, 2019

Introduction Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa,... more Introduction Although most individuals with sickle cell disease (SCD) live in sub-Saharan Africa, the history of the disease on this continent remains largely unknown. SCD is characterized by the association of chronic hemolytic anemia with episodes of acute vaso-occlusive events and progressive vascular organ damage. Several pathophysiological pathways in SCD result in the activation of circulating blood cells and the release of microparticles (MPs). In the present study, we investigated cell-derived MPs in patients with SCD living in Africa and analyzed their relationship with clinical complications. Patients and Methods This cross-sectional case-control study is nested in the CADRE cohort (clinical trials.gov identifier NCTO3114137). We included 232 SS adults in two African centers: Bamako (Mali) and Dakar (Senegal). Patients were chosen depending on the absence or the presence of at least one of the following complications: tricuspid regurgitant jet velocity (TRJV) >3 m/s (wh...

Research paper thumbnail of Effects of Poloxamer 188 on Red Blood Cells Membrane Properties in Sickle Cell Disease

Blood, 2015

Introduction: Sickle cell anemia (SCA) is a severe monogenic hereditary disorder characterized by... more Introduction: Sickle cell anemia (SCA) is a severe monogenic hereditary disorder characterized by chronic hemolytic anemia and the occurrence of frequent painful vaso-occlusive crises (VOC). SCA classical physiological scheme involves hemoglobin S polymerization under hypoxic conditions, which triggers red blood cells (RBCs) sickling. Recent studies demonstrated that the degree of hemorheological alterations, such as blood hyper-viscosity, determines the risk for VOC. Moreover, sickle RBCs abnormally adhere to the vascular endothelium, triggering microvascular occlusions. Despite extensive research very few drugs are available to efficiently treat VOCs or VOC-like events. A first clinical trial was performed to test the efficacy of poloxamer 188 (P188) in a large sickle cell cohort of adults and children (Orringer et al., 2001). This study demonstrated a significant reduction of pain duration in the children treated with P188. Recently, a new phase III multi-center trial has been st...

Research paper thumbnail of The Endothelin Receptor Etb Plays a Crucial Role for Recruitment of Neutrophils to the Vascular Wall in Sickle Cell Disease

Blood, 2016

Introduction: Although Sickle Cell Disease (SCD) is due to abnormal hemoglobin, many cell types, ... more Introduction: Although Sickle Cell Disease (SCD) is due to abnormal hemoglobin, many cell types, including endothelial cells and polymorphonuclear neutrophils (PMNs), play a key role in the pathophysiology of the disease, particularly in the vaso-occlusive events. Adhesion of PMNs to activated endothelium is critical in SCD and might contribute to vaso-occlusion; thus targeting PMN interactions with the endothelium may represent a good opportunity for new therapeutics. We looked for candidate mediators that may be involved in PMN activation and recruitment in tissues. We focused on endothelin-1 (ET-1) since (i) high levels of cytokines have been reported in SCD patients; (ii) we previously demonstrated that ET-1 receptors blockade in the SAD mouse model of SCD leads to reversal or prevention of vaso-occlusive events, nitrative stress, kidney and lung damage, and even death. While demonstrating that ET receptor (ETR) antagonism inhibited a tonic ET-1-dependent vasoconstriction during...

Research paper thumbnail of Rh blood group antigens: from antenatal diagnosis of haemolytic disease of the new born to ammonium transport function

Hematologie, Sep 1, 2004

Le systeme RH (rhesus) est un des systemes de groupe sanguin les plus immunogenes et les plus pol... more Le systeme RH (rhesus) est un des systemes de groupe sanguin les plus immunogenes et les plus polymorphes chez l’homme. Les bases moleculaires de la grande majorite des phenotypes Rh, y compris le phenotype Rh null associe a une anemie hemolytique de severite variable, sont aujourd’hui elucidees. En particulier, la demonstration que le locus RH des individus RhD-positifs est compose des genes RHD et RHCE alors que celui des individus RhD-negatifs ne possede, tout du moins dans la population caucasienne, que le gene RHCE, a permis le developpement d’un diagnostic antenatal des grossesses a risque de maladie hemolytique du nouveau-ne par des tests PCR invasifs (ADN de cellules amniotiques) et non invasifs (ADN fœtal circulant dans le plasma maternel). Les antigenes Rh sont presents dans la membrane du globule rouge au sein du « complexe Rh » forme de l’association des proteines Rh (D et/ou CE), RhAG (Rh associated glycoprotein), LW (ICAM-4), CD47 (IAP) et glycophorine B (GPB). Le complexe Rh serait lui-meme associe a l’echangeur d’anions AE1 (Bande 3). Grâce a ses interactions avec les proteines adaptatrices 4.2 et ankyrine, il contribue a la stabilite et au maintien des proprietes mecaniques de la membrane erythrocytaire. Ainsi, les deficits primaires en proteines Rh ou RhAG, ankyrine ou proteine 4.2 sont tous associes a des spherocytoses hereditaires, typiques ou atypiques. Au-dela de ses deux membres erythroides, Rh et RhAG, la famille des proteines Rh comprend chez les mamiferes deux membres non erythroides, RhBG et RhCG, exprimes essentiellement dans des organes impliques dans la production et l’excretion d’ammonium comme le foie et le rein. Des analyses fonctionnelles dans des systemes d’expression heterologues ou dans des globules rouges de variants naturels ont permis de demontrer que les proteines RhAG, RhBG et RhCG peuvent fonctionner comme des transporteurs d’ammonium (NH 3 et/ou NH 4 +). Ces transporteurs specifiques d’ammonium, les premiers identifies a ce jour chez les mammiferes, pourraient ainsi participer a l’elimination de la charge acide quotidienne generee par le metabolisme. L’ensemble de ces resultats designe les proteines Rh comme de nouveaux elements cles de la structure et de la fonction de la membrane des cellules erythroides et epitheliales.

Research paper thumbnail of Les antigènes de groupe sanguin Rh : du diagnostic anténatal de la maladie hémolytique du nouveau-né à la fonction de transport d’ammonium

Hematologie, Sep 1, 2004

Le systeme RH (rhesus) est un des systemes de groupe sanguin les plus immunogenes et les plus pol... more Le systeme RH (rhesus) est un des systemes de groupe sanguin les plus immunogenes et les plus polymorphes chez l’homme. Les bases moleculaires de la grande majorite des phenotypes Rh, y compris le phenotype Rh null associe a une anemie hemolytique de severite variable, sont aujourd’hui elucidees. En particulier, la demonstration que le locus RH des individus RhD-positifs est compose des genes RHD et RHCE alors que celui des individus RhD-negatifs ne possede, tout du moins dans la population caucasienne, que le gene RHCE, a permis le developpement d’un diagnostic antenatal des grossesses a risque de maladie hemolytique du nouveau-ne par des tests PCR invasifs (ADN de cellules amniotiques) et non invasifs (ADN fœtal circulant dans le plasma maternel). Les antigenes Rh sont presents dans la membrane du globule rouge au sein du « complexe Rh » forme de l’association des proteines Rh (D et/ou CE), RhAG (Rh associated glycoprotein), LW (ICAM-4), CD47 (IAP) et glycophorine B (GPB). Le complexe Rh serait lui-meme associe a l’echangeur d’anions AE1 (Bande 3). Grâce a ses interactions avec les proteines adaptatrices 4.2 et ankyrine, il contribue a la stabilite et au maintien des proprietes mecaniques de la membrane erythrocytaire. Ainsi, les deficits primaires en proteines Rh ou RhAG, ankyrine ou proteine 4.2 sont tous associes a des spherocytoses hereditaires, typiques ou atypiques. Au-dela de ses deux membres erythroides, Rh et RhAG, la famille des proteines Rh comprend chez les mamiferes deux membres non erythroides, RhBG et RhCG, exprimes essentiellement dans des organes impliques dans la production et l’excretion d’ammonium comme le foie et le rein. Des analyses fonctionnelles dans des systemes d’expression heterologues ou dans des globules rouges de variants naturels ont permis de demontrer que les proteines RhAG, RhBG et RhCG peuvent fonctionner comme des transporteurs d’ammonium (NH 3 et/ou NH 4 +). Ces transporteurs specifiques d’ammonium, les premiers identifies a ce jour chez les mammiferes, pourraient ainsi participer a l’elimination de la charge acide quotidienne generee par le metabolisme. L’ensemble de ces resultats designe les proteines Rh comme de nouveaux elements cles de la structure et de la fonction de la membrane des cellules erythroides et epitheliales.