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Fetal and neonatal allo-immune thrombocytopenia (FNAIT) is considered as a rare disease due to the incidence (1/1000-1/2000 births). The major complication of severe thrombocytopenia is bleeding and particularly intra-cranial hemorrhage and neurologic sequelae following. Serology and molecular biology developments have reconfigured the platelet immunology diagnosis. Anti-HPA-1a allo-immunisation is responsible for more than 80% FNAIT cases with a high recurrence rate of severe bleeding complications. Therapeutic management has changed over the coming years from an invasive concept associating fetal blood sampling and in utero platelet transfusion to a non invasive treatment by intravenous immunoglobulins injection (IVIg). The purpose of this article is to provide an update on FNAIT management in the light of current developments over the past 30. years. © 2017.

Garraud O.,Sanguine | Garraud O.,Jean Monnet University | Cognasse F.,Jean Monnet University
Frontiers in Immunology | Year: 2015

Small fragments circulating in the blood were formally identified by the end of the nineteenth century, and it was suggested that they assisted coagulation via interactions with vessel endothelia. Wright, at the beginning of the twentieth century, identified their bone-marrow origin. For long, platelets have been considered sticky assistants of hemostasis and pollutants of blood or tissue samples; they were just cell fragments. As such, however, they were acknowledged as immunizing (to specific HPA and HLA markers): the platelet's dark face. The enlightened face showed that besides hemostasis, platelets contained factors involved in healing. As early as 1930s, platelets entered the arsenal of medicines were transfused, and were soon manipulated to become a kind of glue to repair damaged tissues. Some gladly categorized platelets as cells but they were certainly not fully licensed as such for cell physiologists. Actually, platelets possess almost every characteristic of cells, apart from being capable of organizing their genes: they have neither a nucleus nor genes. This view prevailed until it became evident that platelets play a role in homeostasis and interact with cells other than with vascular endothelial cells; then began the era of physiological and also pathological inflammation. Platelets have now entered the field of immunity as inflammatory cells. Does assistance to immune cells itself suffice to license a cell as an "immune cell"? Platelets prove capable of sensing different types of signals and organizing an appropriate response. Many cells can do that. However, platelets can use a complete signalosome (apart from the last transcription step, though it is likely that this step can be circumvented by retrotranscribing RNA messages). The question has also arisen as to whether platelets can present antigen via their abundantly expressed MHC class I molecules. In combination, these properties argue in favor of allowing platelets the title of immune cells. © 2015 Garraud and Cognasse.

Canellini G.,Sanguine
Blood transfusion = Trasfusione del sangue | Year: 2012

The storage of blood induces the formation of erythrocytes-derived microparticles. Their pathogenic role in blood transfusion is not known so far, especially the risk to trigger alloantibody production in the recipient. This work aims to study the expression of clinically significant blood group antigens on the surface of red blood cells microparticles. Red blood cells contained in erythrocyte concentrates were stained with specific antibodies directed against blood group antigens and routinely used in immunohematology practice. After inducing erythrocytes vesiculation with calcium ionophore, the presence of blood group antigens was analysed by flow cytometry. The expression of several blood group antigens from the RH, KEL, JK, FY, MNS, LE and LU systems was detected on erythrocyte microparticles. The presence of M (MNS1), N (MNS2) and s (MNS4) antigens could not be demonstrated by flow cytometry, despite that glycophorin A and B were identified on microparticles using anti-CD235a and anti-MNS3. We conclude that blood group antigens are localized on erythrocytes-derived microparticles and probably keep their immunogenicity because of their capacity to bind specific antibody. Selective segregation process during vesiculation or their ability to elicit an immune response in vivo has to be tested by further studies.

Sureau C.,Sanguine
Methods in molecular biology (Clifton, N.J.) | Year: 2010

Worldwide, it is estimated that more than 350 million people are chronically infected with hepatitis B virus (HBV), approximately 15 million of whom are coinfected with hepatitis D virus (HDV), a satellite of HBV that uses the envelope proteins of the latter to assemble its infectious particles. For a long time after HBV discovery, research on the viral life cycle, viral entry in particular, has been hampered by the lack of practical tissue culture systems. To date, in vitro isolation and serial propagation of HBV are still problematic, but the examination of the entire HBV life cycle is possible using two separate systems: (i) permissive human hepatoma cell lines to study HBV DNA replication, viral transcription, translation, assembly, and release of viral particles and (ii) primary cultures of human or chimpanzee hepatocytes or the susceptible HepaRG cell line for viral entry examination. The experimental model described here for analyzing the function of HBV envelope proteins at viral entry is based on this dual tissue culture system, in which HDV is substituted to HBV for practical reasons.

Blanchet M.,INRS - Institute National de la Recherche Scientifique | Sureau C.,Sanguine | Labonte P.,INRS - Institute National de la Recherche Scientifique
Antiviral Research | Year: 2014

Worldwide there are approximately 240 million individuals chronically infected with the hepatitis B virus (HBV), including 15-20 million coinfected with the hepatitis delta virus (HDV). Treatments available today are not fully efficient and often associated to important side effects and development of drug resistance. Targeting the HBV/HDV entry step using preS1-specific lipopeptides appears as a promising strategy to block viral entry for both HBV and HDV (Gripon et al., 2005; Petersen et al., 2008). Recently, the human Sodium Taurocholate Cotransporting Polypeptide (hNTCP) has been identified as a functional, preS1-specific receptor for HBV and HDV. This groundbreaking discovery has opened a very promising avenue for the treatment of chronic HBV and HDV infections. Here we investigated the ability of FDA approved therapeutics with documented inhibitory effect on hNTCP cellular function to impair viral entry using a HDV in vitro infection model based on a hNTCP-expressing Huh7 cell line. We demonstrate the potential of three FDA approved molecules, irbesartan, ezetimibe, and ritonavir, to alter HDV infection in vitro. © 2014 Elsevier Ltd. All rights reserved.

Tissot J.-D.,Sanguine | Rubin O.,Sanguine | Canellini G.,Sanguine
Current Opinion in Hematology | Year: 2010

Purpose of Review: The mechanisms involved in the formation of red blood cell (RBC) microparticles in vivo as well as during erythrocyte storage are reviewed, and the potential role of microparticles in transfusion medicine is described. Recent Findings: Microparticles release is an integral part of the erythrocyte ageing process, preventing early removal of RBCs. Proteomics analyses have outlined the key role of band 3-ankyrin anchoring complex and the occurrence of selective RBC membrane remodelling mechanisms in microparticles formation. The presence of several RBC antigens, expressed on microparticles, has been demonstrated. The potential deleterious effects of RBC microparticles in transfused recipients, including hypercoagulability, microcirculation impairment and immunosuppression, are discussed. Summary: Formation and role of RBC microparticles are far from being completely understood. Combining various approaches to elucidate these mechanisms could improve blood product quality and transfusion safety. Implementation of RBC microparticles as biomarkers in the laboratory routine needs to overcome technical barriers involved in their analysis. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Bertrand G.,Sanguine | Drame M.,University of Reims Champagne Ardenne | Martageix C.,Sanguine | Kaplan C.,Sanguine
Blood | Year: 2011

Fetal/neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia in the fetus and in an otherwise healthy newborn. To counter the consequences of severe fetal thrombocytopenia, antenatal therapies have been implemented. Predictive parameters for fetal severe thrombocytopenia are important for the development of noninvasive strategy and tailored intervention. We report here data concerning 239 pregnancies in 75 HPA-1bb women. Analysis of the index cases (diagnosis of fetal/neonatal alloimmune thrombocytopenia) did not show any significant correlation between the severity of the disease and the maternal genetic background (ABO blood group and HLA-DRB3 allele). Subsequent pregnancies were managed, and therapy effectiveness was evaluated. The highest mean newborn platelet count was observed for a combination of intravenous immunoglobulin and steroids (135 × 10 9/L; 54 newborns) compared with intravenous immunoglobulin alone (89 × 109/L; 27 newborns). The maternal anti-HPA-1a antibody concentration measured before any treatment and before 28 weeks of gestation was predictive of the fetal status. The weighted areas under curves of the maternal alloantibody concentrations were predictive of therapy response. To conclude, this large retrospective survey gives new insights on maternal predictive parameters for fetal status and therapy effectiveness allowing noninvasive strategies. © 2011 by The American Society of Hematology.

Sanguine, University of the French West Indies and Guiana | Date: 2014-02-04

The present invention relates to methods for assaying JAK2 activity in a red blood cell. The present invention also relates to methods for diagnosing myeloproliferative neoplasm.

University of the French West Indies, Guiana and Sanguine | Date: 2014-03-04

The present invention relates to isolated VHHs directed against human Glycophorin A. The present invention also relates to fusion proteins comprising the VHH according to the invention that is fused to at least one heterologous polypeptide and immunoconjugates comprising the VHH according to the invention that is conjugated to at least one chemical compound and their use in therapeutic or diagnostic methods.

News Article | February 24, 2013

Led by Brian Neman, CEO, Sanguine BioSciences is a biotechnology company that aims to provide transparency throughout the personalized medicine R&D process. It collects and de-identifies patient-derived data in the form of biospecimen and physician and self-reported information. These data are generated and then made available to researchers involved in drug and biomarker research and discovery. The company intends to use the capital to further develop their internal infrastructure in order to efficiently collect, process, document, and store up to 1,000 blood samples each month across the west coast.

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