Éditeur(s) : HAL CCSD EDP Sciences
Résumé : International audience
This paper presents a comparison of models for extreme rainfall and flood values. Based on a large set of thousands of rainfall and discharge data, the French ExtraFlo project showed that design estimate of extreme values based on the fitting of a distribution on a limited sample of maximum values is very inaccurate when only a few decades of observation are available. Some interesting alternatives are possible, using a regional approach, or historical data when available, or simulation methods, or sedimentological or geochemical signatures of flood deposits.
Cette communication présente les principaux résultats du projet ExtraFlo sur l'estimation des pluies et crues extrêmes. A partir d'un jeu de données conséquent de plusieurs milliers de stations, une procédure d'inter-comparaison a permis d'évaluer les performances d'une trentaine d'implémentations différentes issues de différentes combinaisons (modèle probabiliste, méthode d'estimation, cadre local / régional / mixte local et régional). Le projet ExtraFlo a permis de mettre en évidence le manque de robustesse des approches basées sur le traitement statistique d'une série de quelques dizaines d'années d'observation. Des alternatives intéressantes existent, basées sur l'exploitation des records de pluie et de débit à l'échelle d'une région, de la collecte de données historiques quand cela est possible, de méthodes de simulation basées sur le couplage d'un générateur d'averses avec un modèle hydrologique pour la transformation des pluies en débit, ou des traces morphologiques laissées par les crues anciennes.
ISSN: 0018-6368

hal-01128341
https://hal.archives-ouvertes.fr/hal-01128341
https://hal.archives-ouvertes.fr/hal-01128341/document
https://hal.archives-ouvertes.fr/hal-01128341/file/ly2014-pub00041933.pdf
DOI : 10.1051/lhb/2014010

Éditeur(s) : HAL CCSD
Résumé : International audience
Sharks International
Durban, South Africa

hal-01487162
http://hal.univ-reunion.fr/hal-01487162

Éditeur(s) : HAL CCSD American Society of Hematology
Résumé : International audience
Polycythemia vera (PV) is characterized by an increased RBC mass, spontaneous erythroid colony formation, and the JAK2V617F mutation. PV is associated with a high risk of mesenteric and cerebral thrombosis. PV RBC adhesion to endothelial laminin is increased and mediated by phosphorylated erythroid Lu/BCAM. In the present work, we investigated the mechanism responsible for Lu/BCAM phosphorylation in the presence of JAK2V617F using HEL and BaF3 cell lines as well as RBCs from patients with PV. High levels of Rap1-GTP were found in HEL and BaF3 cells expressing JAK2V617F compared with BaF3 cells with wild-type JAK2. This finding was associated with increased Akt activity, Lu/BCAM phosphorylation, and cell adhesion to laminin that were inhibited by the dominant-negative Rap1S17N or by the specific Rap1 inhibitor GGTI-298. Surprisingly, knocking-down EpoR in HEL cells did not alter Akt activity or cell adhesion to laminin. Our findings reveal a novel EpoR-independent Rap1/Akt signaling pathway that is activated by JAK2V617F in circulating PV RBCs and responsible for Lu/BCAM activation. This new characteristic of JAK2V617F could play a critical role in initiating abnormal interactions among circulating and endothelial cells in patients with PV.
ISSN: 0006-4971

inserm-00821109
http://www.hal.inserm.fr/inserm-00821109
http://www.hal.inserm.fr/inserm-00821109/document
http://www.hal.inserm.fr/inserm-00821109/file/De_Grandis_Blood_2013.pdf
DOI : 10.1182/blood-2012-07-440487

Éditeur(s) : HAL CCSD John Libbey Eurotext
Résumé : International audience
Environmental health risk assessment is commonly used in France for risk management purposes. The Methodology section of the "Société française de santé environnement" (French Society for Environmental Health) seeks to improve the utility and implementation of risk assessment in France. An initial operational objective is to make a list of short-, intermediate- and long-term improvements. This inventory is based in part on the experience and expertise of society members in this area and in part on their analysis of "Science and Decisions: Advancing Risk Assessment" (National Research Council 2009). In this paper, the Society recommends modifications in the indications for and use of risk assessments, during each of the four stages of the process: hazard identification and dose-response assessment, exposure assessment, risk characterization, and results interpretation. Some may be implemented now, while others need consensus building or research because of gaps in knowledge. Environmental health risk assessment must be understood as a decision tool for risk management in situations of uncertainly. Thus, appropriate linkage is required between decision making and assessment, and between the methods and the expected results.
L'évaluation des risques sanitaires est fréquemment utilisée en France dans les processus de décision en santé environnementale. La section " Méthodologie d'évaluation des risques sanitaires " de la Société française de santé environnement (SFSE) s'est donnée pour objectif de proposer des éléments de réflexion et des outils méthodologiques en vue d'améliorer l'utilité et les pratiques de l'évaluation des risques sanitaires. Un premier objectif opérationnel est l'inventaire des améliorations possibles à court, moyen et long termes à apporter à la démarche et à son utilisation. Ce travail s'est fondé, d'une part, sur la pratique et l'expertise des membres de la section, et, d'autre part, sur une lecture critique du rapport " Science and Decisions : Advancing Risk Assessment " publié en 2009 par le National Research Council et portant également sur les évolutions de la démarche. Dans cet article, la section restitue les conclusions de cet inventaire critique et propose un certain nombre d'améliorations en termes d'indications et d'utilisations de l'évaluation des risques sanitaires pour chacune des quatre étapes : identification des dangers et relation dose-réponse ; évaluation de l'exposition ; caractérisation des risques ; et interprétation des résultats. Certaines recommandations peuvent être mises en oeuvre immédiatement ; d'autres, en préalable à leur mise en oeuvre, nécessitent un consensus ou encore de la recherche car les connaissances manquent. En conclusion, la section insiste sur le fait que l'évaluation des risques sanitaires doit être comprise comme une aide à la décision en situation d'incertitude ; l'articulation entre le contexte décisionnel et l'évaluation, sa méthodologie et les résultats attendus est donc primordiale.
ISSN: 1635-0421

ineris-00963325
https://hal-ineris.archives-ouvertes.fr/ineris-00963325
DOI : 10.1684/ers.2011.0435
INERIS : EN-2012-016

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
ISSN: 0007-1048

hal-01668324
https://hal.univ-antilles.fr/hal-01668324
DOI : 10.1111/bjh.14064

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 Météo et Climat
Résumé : International audience
D'initiative française, le projet international HyMeX a pour objectif d'améliorer la compréhension du cycle de l'eau en Méditerranée, de sa variabilité, de l'échelle de l'événement météorologique aux échelles saisonnières et interannuelles, et de ses caractéristiques sur une décennie, dans un contexte de changement global. Le projet est motivé par le rôle déterminant des processus de mésoéchelle, couplés entre l'atmosphère, la mer et la terre, sur la variabilité du système climatique et sur le déclenchement d'événements hydrométéorologiques extrêmes (précipitations et inondations, vents forts et convection océanique, canicules et sécheresses). Le projet vise enfin à évaluer les conséquences de ces événements extrêmes sur la vulnérabilité sociale et économique de cette région et sa capacité d'adaptation.
ISSN: 0026-1181

hal-00828758
https://hal.archives-ouvertes.fr/hal-00828758
https://hal.archives-ouvertes.fr/hal-00828758/document
https://hal.archives-ouvertes.fr/hal-00828758/file/meteo_2013_80_23%20%281%29.pdf
DOI : 10.4267/2042/48792

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
A decreased global autonomic nervous system (ANS) activity and increased sympathetic activation in patients with sickle cell anemia (SCA) seem to worsen the clinical severity and could play a role in the pathophysiology of the disease, notably by triggering vaso-occlusive crises. Because exercise challenges the ANS activity in the general population, we sought to determine whether a short (,15 min) and progressive moderate exercise session conducted until the first ventilatory threshold had an effect on the ANS activity of a group of SCA patients and a group of healthy individuals (CONT group). Temporal and spectral analyses of the nocturnal heart rate variability were performed before and on the 3 nights following the exercise session. Standard deviation of all normal RR intervals (SDNN), total power, low frequencies (LF) and high frequencies powers (HF) were lower but LF/HF was higher in SCA patients than in the CONT group. Moderate exercise did not modify ANS activity in both groups. In addition, no adverse clinical events occurred during the entire protocol. These results imply that this kind of short and moderate exercise is not detrimental for SCA patients.
ISSN: 1932-6203

hal-01136725
https://hal.univ-antilles.fr/hal-01136725
https://hal.univ-antilles.fr/hal-01136725/document
https://hal.univ-antilles.fr/hal-01136725/file/Hedreville%20et%20al.%20-%202014%20-%20Acute%20moderate%20exercise%20does%20not%20further%20alter%20the%20autonomic%20nervous%20system%20activity%20in%20patients%20with%20sick%282%29.pdf
DOI : 10.1371/journal.pone.0095563

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Hemorheological abnormalities have been well characterized in sickle cell disease (SCD) and seem to modulate the clinical severity [1]. For instance, increased blood viscosity raises the risk for frequent vaso-occlusive crisis (VOC) and increased red blood cell (RBC) aggregates robustness (i.e., RBC disaggregation threshold) enhances the risks for acute chest syndrome (ACS) [2]. Moreover, patients with the most rigid RBCs are characterized by high hemolytic rate, which increases the risks to develop leg ulcers or glomerulopathy [3]. However, except few studies supporting an effect of alpha-thalassemia and oxidative stress [1] on RBC rheological properties of SCD patients, very few experiments focused on the genetic and cellular factors modulating blood rheology in this disease.
ISSN: 1079-9796

hal-01263890
https://hal.archives-ouvertes.fr/hal-01263890
https://hal.archives-ouvertes.fr/hal-01263890/document
https://hal.archives-ouvertes.fr/hal-01263890/file/Ferdinand%20et%20al.%20eNOS%20and%20RBC%20rheology%20in%20SCD_BCMD.pdf
PUBMED : 26142331

Éditeur(s) : HAL CCSD Wiley
Résumé : International audience
BACKGROUND: The RH blood group system has many RHCE variant alleles that have arisen through gene conversion or nucleotide changes. Two probands, with red blood cells (RBCs) that were D+C+E-c+(w) e+ were sent to our laboratories to resolve the weak c expression. STUDY DESIGN AND METHODS: Hemagglutination tests were performed by automated and manual procedures. Genomic DNA analysis was performed by sequencing of Exons 1 to 10 of RHCE and RHD. RESULTS: The probands' RBCs did not react with standard monoclonal anti-E reagents from Bio-Rad, Diagast, DiaMed, Immucor, Ortho, and Quotient. The RBCs reacted variably with anti-c reagents from Diagast, DiaMed, Immucor, or Ortho and did not react with the Quotient anti-c reagent. Surprisingly, sequencing results of RHCE showed the presence of C/G at Position 676 (E/e polymorphism) and the association of the E polymorphism with a 734T>C transition in Exon 5 of the RHCE, encoding a Leu245Pro amino acid substitution in the mature RhcE polypeptide. Replacement of leucine 245 by proline in the eighth transmembrane domain of the RhcE protein may have a steric effect on the protein such that most anti-E reagents do not bind and the interaction between anti-c and c antigen is also affected. CONCLUSION: We report a novel RHCE*cE allele, RHCE*cE734C, which was assigned the provisional ISBT allele name RHCE*cE.14 or RHCE*03.14. It was found in two probands whose RBCs had weakened c expression and typed E- with conventional anti-E reagents. These data, once again, highlight the fact that the genotype does not always reflect the phenotype.
ISSN: 0041-1132

hal-00839022
https://hal.archives-ouvertes.fr/hal-00839022
DOI : 10.1111/j.1537-2995.2012.03860.x
PUBMED : 22958092

Éditeur(s) : HAL CCSD IOS Press
Résumé : International audience
The hematocrit-to-viscosity ratio (HVR) has been widely used has an estimate of red blood cell (RBC) oxygen transport effectiveness into the microvasculature or as an oxygen delivery index. However, no study investigated the possibility of HVR to truly reflect RBC oxygen transport effectiveness or to be an oxygen delivery index. We measured blood viscosity at high shear rate (225 s-1), hematocrit, HVR, as well as the microvascular oxyhemoglobin saturation (TOI; tissue oxygen index) by spatial resolved near-infrared spectroscopy (NIRS) at cerebral and muscle levels in three population known to have various degrees of hemorheological abnormalities: healthy subjects (AA), patients with sickle cell SC disease (SC) characterized by moderate anemia and patients with sickle cell anemia (SS) marked by severe anemia. At both the cerebral and muscle level, HVR was positively correlated with TOI (r = 0.28; p = 0.03 and r = 0.38; p = 0.003, at the cerebral and muscle level, respectively). These findings suggest that HVR probably play a key role in blood flow and hemodynamic regulation in the microvasculature, hence modulating the amount of oxygen available for tissues. Nevertheless, the strengths of the associations are weak (R2 < 0.50), suggesting that other determinants modulate microvascular blood flow and oxygenation, such as vascular geometry and vasomotor reserve.
ISSN: 1386-0291

inserm-01081701
http://www.hal.inserm.fr/inserm-01081701
http://www.hal.inserm.fr/inserm-01081701/document
http://www.hal.inserm.fr/inserm-01081701/file/2013%2C%20Waltz%20-%20Is%20there%20a%20relationship%20between%20the%20hematocrit-to-viscosity%20ratio%20and%20microvascular%20oxygenation%20in%20brain%20and%20muscle.pdf
PUBMED : 23719422

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Dudley et al. [9] commented on our paper [11], arguing that the current IUCN objective-based categorization ofprotected areas, which is also used in marine protected areas (MPAs), should not be abandoned and replaced bythe new regulation-based classification system [11]. Here we clarify that we do not advocate replacing thecurrent IUCN categories, but highlight the benefits of using both the objective-based IUCN categories and thenew regulation-based classification when applied to MPAs. With an increasing number of MPA types beingimplemented, most of them multiple-use areas zoned for various purposes, assessing ecological and socioeconomicbenefits is key for advancing conservation targets and policy objectives. Although the IUCN categoriescan be used both in terrestrial and marine systems, they were not designed to follow a gradient of impacts andthere is often a mismatch between stated objectives and implemented regulations. The new regulation-basedclassification system addresses these problems by linking impacts of activities in marine systems with MPA andzone classes in a simple and globally applicable way. Applying both the IUCN categories and the regulationbasedclasses will increase transparency when assessing marine conservation goals.
ISSN: 0308-597X

hal-01469541
https://hal-univ-perp.archives-ouvertes.fr/hal-01469541
DOI : 10.1016/j.marpol.2016.11.025

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 Ferrata Storti Foundation
Résumé : International audience
Lionnet et al. recently reported a high prevalence of retinopathy (RET) and otologic disorders (OTD) in patients with sickle cell-hemoglobin C disease (SC), while a significant number of patients had renal diseases (mainly glomerulopathy; GLO) and osteonecrosis (OST). The pathophysiological processes of these complications in SC are not well defined, although blood hyperviscosity has been suspected, but never tested to the best of our knowledge, as responsible for several chronic complications in SC disease1,2. The aim of this study was to analyze the associations between hematological and hemorheological parameters and chronic complications in adult SC patients.
ISSN: 0390-6078

inserm-01081709
http://www.hal.inserm.fr/inserm-01081709
http://www.hal.inserm.fr/inserm-01081709/document
http://www.hal.inserm.fr/inserm-01081709/file/2014%2C%20Lemonne%20-%20Impaired%20blood%20rheology%20plays%20a%20role%20in%20the%20chronic%20disorders%20associated%20with%20sickle%20cell-hemoglobin%20C%20disease.pdf
PUBMED : 24633868

Éditeur(s) : HAL CCSD Inter-Research
Résumé : International audience
Ecological connectivity is important for effective marine planning and biodiversity conservation. Our aim was to identify factors important in influencing variation in benthic community structure on shallow rocky reefs in 2 regions of the Mediterranean Sea with contrasting oceanographic regimes. We assessed beta (β) diversity at 146 sites in the littoral and shallow sub-littoral from the Adriatic/Ionian Seas (eastern region) and Ligurian/Tyrrhenian Seas (western region) using a null modelling approach to account for variation in species richness. The distance decay relationship between species turnover within each region and geographic distance by sea was determined using generalised linear models. Mantel tests were used to examine correlations between β diversity and connectivity by ocean currents, estimated from Lagrangian dispersal simulations. Variation in β diversity between sites was partitioned according to environmental and spatial components using a distance-based redundancy approach. Species turnover along a gradient of geographic distance was greater by a factor of 3 to 5 in the western region than the eastern region, suggesting lower con-nectivity between sites. β diversity was correlated with connectivity by ocean currents at both depths in the eastern region but not in the western region. The influence of spatial and environmental predictors of β diversity varied considerably between regions, but was similar between depths. Our results highlight the interaction of oceanographic, spatial and environmental processes influencing benthic marine β diversity. Persistent currents in the eastern region may be responsible for lower observed β diversity compared to the western region, where patterns of water circulation are more variable.
Marine Ecology Progress Series

Droits : http://creativecommons.org/licenses/by/
hal-01357935
https://hal-univ-perp.archives-ouvertes.fr/hal-01357935
https://hal-univ-perp.archives-ouvertes.fr/hal-01357935/document
https://hal-univ-perp.archives-ouvertes.fr/hal-01357935/file/m553p001.pdf
DOI : 10.3354/meps11783

Éditeur(s) : HAL CCSD
Résumé : International audience
The Duffy Antigen/Receptor for Chemokine (DARC) is a seven segment transmembrane protein. It was firstly discovered as a blood group antigen and was the first specific gene locus assigned to a specific autosome in man. It became more famous as an erythrocyte receptor for malaria parasites (Plasmodium vivax and Plasmodium knowlesi), and finally for chemokines. DARC is an unorthodox chemokine receptor as (i) it binds chemokines of both CC and CXC classes and (ii) it lacks the Asp-Arg-Tyr consensus motif in its second cytoplasmic loop hence cannot couple to G proteins and activate their signaling pathways. DARC had also been associated to cancer progression, numerous inflammatory diseases, and possibly to AIDS. In this review, we will summarize important biological data on DARC. Then we shall focus on recent development of the elaboration and analyzes of structural models of DARC. We underline the difficulty to propose pertinent structural models of transmembrane protein using comparative modeling process, and other dedicated approaches as the Protein Blocks. The chosen structural models encompass most of the biochemical data known to date. Finally, we present recent development of protein - protein docking between DARC structural models and CXCL-8 structures. We propose a hierarchal search based on separated rigid and flexible docking.
Infectious disorders drug targets

Droits : info:eu-repo/semantics/OpenAccess
inserm-00366309
http://www.hal.inserm.fr/inserm-00366309
http://www.hal.inserm.fr/inserm-00366309/document
http://www.hal.inserm.fr/inserm-00366309/file/de_Brevern_Autin_Bertrand_Colin_Etchebest.pdf
http://www.hal.inserm.fr/inserm-00366309/file/inserm-00366309_edited.pdf

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
We studied the diversity within the former genus Gymnangium in the South West IndianOcean by using an integrative approach of both traditional (morphology-based) and modernmolecular taxonomy. Nine species were recorded in the material collected. A total of 97 16Smitochondrial DNA sequences and 54 Calmodulin nuclear sequences from eight Gymnangium/Taxella species were analyzed. We found both morphological and molecular differencesin the studied Gymnangium species that make it necessary to split the genus. It isproposed to revalidate the genus Taxella which is currently regarded as a synonym ofGymnangium. Two species of the genus Taxella (T. eximia and T. gracilicaulis), until nowregarded as distinct species based on morphological characteristics, cluster together in onephylogenetic clade. Possible explanations are discussed. Two species from Madagascarnew to science are herein described and rare species from the Indian Ocean islands are redescribed.
ISSN: 1932-6203

hal-01564043
https://hal-univ-perp.archives-ouvertes.fr/hal-01564043
DOI : 10.1371/journal.pone.0174244

Éditeur(s) : HAL CCSD EDP Sciences
Résumé : Cette communication présente les principaux résultats du projet ExtraFlo sur l'estimation des pluies et crues extrêmes. A partir d'un jeu de données conséquent de plusieurs milliers de stations, une procédure d'inter-comparaison a permis d'évaluer les performances d'une trentaine d'implémentations différentes issues de différentes combinaisons (modèle probabiliste, méthode d'estimation, cadre local / régional / mixte local et régional). Le projet ExtraFlo a permis de mettre en évidence le manque de robustesse des approches basées sur le traitement statistique d'une série de quelques dizaines d'années d'observation. Des alternatives intéressantes existent, basées sur l'exploitation des records de pluie et de débit à l'échelle d'une région, de la collecte de données historiques quand cela est possible, de méthodes de simulation basées sur le couplage d'un générateur d'averses avec un modèle hydrologique pour la transformation des pluies en débit, ou des traces morphologiques laissées par les crues anciennes.
ISSN: 0018-6368

hal-01054313
https://hal.archives-ouvertes.fr/hal-01054313
DOI : 10.1051/1hb/2014010

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Sickle cell anemia (SCA) and hemoglobin SC (HbSC) disease are the two most common forms of sickle cell disease (SCD), a frequent hemoglobinopathy which exhibits a highly variable clinical course. Although high levels of microparticles (MPs) have been consistently reported in SCA and evidence of their harmful impact on the SCA complication occurrences have been provided, no data on MP pattern in HbSC patients has been reported so far. In this study, we determined and compared the MP patterns of 84 HbSC and 96 SCA children, all at steady-state, using flow cytometry. Most of circulating MPs were derived from platelets (PLTs) and red blood cells (RBCs) in the two SCD syndromes. Moreover, we showed that HbSC patients exhibited lower blood concentration of total MPs compared to SCA patients, resulting mainly from a decrease of MP levels originated from RBCs and to a lesser extent from PLTs. We did not detect any association between blood MP concentrations and the occurrence of painful vaso-occlusive crises, acute chest syndrome and pulmonary hyper-tension in both patient groups. We also demonstrated for the first time, that whatever the considered genotype, RBC-derived MPs exhibited higher externalized phosphatidylserine level and were larger than PLT-derived MPs.
ISSN: 1932-6203

hal-01668322
https://hal.univ-antilles.fr/hal-01668322
https://hal.univ-antilles.fr/hal-01668322/document
https://hal.univ-antilles.fr/hal-01668322/file/journal.pone.0177397.pdf
DOI : 10.1371/journal.pone.0177397

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
A recent study suggested that adenosine signaling pathway could promote hemolysis in patients with sickle cell anemia (SCA). This signaling pathway involves several gene coding enzymes for which variants have been described. In this study, we analyzed the genotype-phenotype relationships between functional polymorphisms or polymorphisms associated with altered expression of adenosine pathway genes, namely adenosine deaminase (ada; rs73598374), adenosine A2b receptor (adora2b; rs7208480), adenylyl cyclase6 (adcy6; rs3730071, rs3730070, rs7300155), and hemolytic rate in SCA patients. One hundred and fifty SCA patients were genotyped for adcy6, ada, and adora2b variants as well as alpha-globin gene, a genetic factor known to modulate hemolytic rate. Hematological and biochemical data were obtained at steady-state. Lactate dehydrogenase, aspartate aminotransferase, reticulocytes and total bilirubin were used to calculate a hemolytic index. Genotype-phenotype relationships were investigated using parametric tests and multivariate analysis. SCA patients carrying at least one allele of adcy6 rs3730070-G exhibited lower hemolytic rate than non-carriers in univariate analysis (p=0.006). The presence of adcy6 rs3730070-G variant was associated with a decreased hemolytic rate in adjusted model for age and alpha-thalassemia (p=0.032). Our results support a protective effect of adcy6 rs3730070-G variant on hemolysis in SCA patients.
ISSN: 1079-9796

hal-01668332
https://hal.univ-antilles.fr/hal-01668332
DOI : 10.1016/j.bcmd.2016.02.006