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261 results on '"Delignat, Sandrine"'

1. Transplacental delivery of therapeutic proteins by engineered immunoglobulin G: a step toward perinatal replacement therapy

Author

Mimoun, Angelina, Bou-Jaoudeh, Melissa, Delignat, Sandrine, Daventure, Victoria, Reyes Ruiz, Alejandra, Lecerf, Maxime, Azam, Aurélien, Noe, Remi, Peyron, Ivan, Christophe, Olivier D., Lenting, Peter J., Proulle, Valérie, McIntosh, Jenny, Nathwani, Amit C., Dimitrov, Jordan D., Denis, Cécile V., and Lacroix-Desmazes, Sébastien

Published
2023
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3. High factor VIII concentrations interfere with glycoprotein VI-mediated platelet activation in vitro

Author

Sekar, Rohini, primary, Mimoun, Angelina, additional, Bou-Jaoudeh, Melissa, additional, Loyau, Stéphane, additional, Delignat, Sandrine, additional, Daventure, Victoria, additional, Bonilla, Perrine, additional, Bhale, Aishwarya Sudam, additional, Venkataraman, Krishnan, additional, Rayes, Julie, additional, Boulaftali, Yacine, additional, Jandrot-Perrus, Martine, additional, Proulle, Valérie, additional, and Lacroix-Desmazes, Sébastien, additional

Published
2024
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4. IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies

Author

Leborgne, Christian, Barbon, Elena, Alexander, Jeffrey M., Hanby, Hayley, Delignat, Sandrine, Cohen, Daniel M., and Collaud, Fanny

Subjects
Gene therapy -- Methods -- Management -- Usage -- Health aspects -- Physiological aspects, Viral antibodies -- Control -- Health aspects -- Methods -- Physiological aspects -- Usage, Immunotherapy -- Physiological aspects -- Health aspects -- Methods -- Usage, Genetic vectors -- Usage -- Methods -- Physiological aspects -- Health aspects, Immunoglobulin G -- Physiological aspects -- Health aspects -- Usage, Antibodies -- Control -- Health aspects -- Methods -- Physiological aspects -- Usage, Company business management, Biological sciences, Health
Abstract

Neutralizing antibodies to adeno-associated virus (AAV) vectors are highly prevalent in humans.sup.1,2, and block liver transduction.sup.3-5 and vector readministration.sup.6; thus, they represent a major limitation to in vivo gene therapy. Strategies aimed at overcoming anti-AAV antibodies are being studied.sup.7, which often involve immunosuppression and are not efficient in removing pre-existing antibodies. Imlifidase (IdeS) is an endopeptidase able to degrade circulating IgG that is currently being tested in transplant patients.sup.8. Here, we studied if IdeS could eliminate anti-AAV antibodies in the context of gene therapy. We showed efficient cleavage of pooled human IgG (intravenous Ig) in vitro upon endopeptidase treatment. In mice passively immunized with intravenous Ig, IdeS administration decreased anti-AAV antibodies and enabled efficient liver gene transfer. The approach was scaled up to nonhuman primates, a natural host for wild-type AAV. IdeS treatment before AAV vector infusion was safe and resulted in enhanced liver transduction, even in the setting of vector readministration. Finally, IdeS reduced anti-AAV antibody levels from human plasma samples in vitro, including plasma from prospective gene therapy trial participants. These results provide a potential solution to overcome pre-existing antibodies to AAV-based gene therapy. An IgG-cleaving endopeptidase can degrade circulating anti-adeno-associated virus antibodies in mice and nonhuman primates in vivo, as well as in human plasma in vitro, offering a potential solution for a major hurdle in gene therapy., Author(s): Christian Leborgne [sup.1] , Elena Barbon [sup.1] , Jeffrey M. Alexander [sup.2] , Hayley Hanby [sup.2] , Sandrine Delignat [sup.3] [sup.4] , Daniel M. Cohen [sup.2] , Fanny Collaud [...]

Published
2020
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8. Natural Antibodies Sustain Differentiation and Maturation of Human Dendritic Cells

Author

Bayry, Jagadeesh, Lacroix-Desmazes, Sébastien, Donkova-Petrini, Vladimira, Carbonneil, Cédric, Misra, Namita, Lepelletier, Yves, Delignat, Sandrine, Varambally, Sooryanarayana, Oksenhendler, Eric, Lévy, Yves, Debré, Marianne, Kazatchkine, Michel D., Hermine, Olivier, Kaveri, Srini V., and Steinman, Ralph M.

Published
2004

9. IdeS, a new option to optimize the management of patients with hemophilia A on emicizumab

Author

Bou-Jaoudeh, Melissa, primary, Mimoun, Angelina, additional, Delignat, Sandrine, additional, Peyron, Ivan, additional, Capdevila, Ladislas, additional, Daventure, Victoria, additional, Deligne, Claire, additional, Dimitrov, Jordan D., additional, Christophe, Olivier D., additional, Denis, Cécile V., additional, Lenting, Peter J., additional, Proulle, Valérie, additional, and Lacroix-Desmazes, Sébastien, additional

Published
2023
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13. Correction of bleeding in experimental severe hemophilia A by systemic delivery of factor VIII-encoding mRNA

Author

Russick, Jules, Delignat, Sandrine, Milanov, Peter, Christophe, Olivier, Boros, Gábor, Denis, Cécile V., Lenting, Peter J., Kaveri, Srinivas V., and Lacroix-Demazes, Sébastien

Subjects
Mice, Factor VIII, hemic and lymphatic diseases, Antibodies, Bispecific, Coagulation & its Disorders, Animals, Humans, Hemorrhage, RNA, Messenger, Hemophilia A, Article
Abstract

The treatment or prevention of bleeding in patients with hemophilia A relies on replacement therapy with different factor VIII (FVIII)-containing products or on the use of by-passing agents, i.e., activated prothrombin complex concentrates or recombinant activated factor VII. Emerging approaches include the use of bispecific anti-factor IXa/factor X antibodies, anti-tissue factor pathway inhibitor antibodies, interfering RNA to antithrombin, and activated protein C-specific serpins or gene therapy. The latter strategies are, however, hampered by the short clinical experience and potential adverse effects including the absence of tight temporal and spatial control of coagulation and the risk of uncontrolled insertional mutagenesis. Systemic delivery of mRNA allows endogenous production of the corresponding encoded protein. Thus, injection of erythropoietin-encoding mRNA in a lipid nanoparticle formulation resulted in increased erythropoiesis in mice and macaques. Here, we demonstrate that a single injection of in vitro transcribed B domain-deleted FVIII-encoding mRNA to FVIII-deficient mice enables endogenous production of pro-coagulant FVIII. Circulating FVIII:C levels above 5% of normal levels were maintained for up to 72 h, with an estimated half-life of FVIII production of 17.9 h, and corrected the bleeding phenotype in a tail clipping assay. The endogenously produced FVIII did however exhibit low specific activity and induced a potent neutralizing IgG response upon repeated administration of the mRNA. Our results suggest that the administration of mRNA is a plausible strategy for the endogenous production of proteins characterized by poor translational efficacy. The use of alternative mRNA delivery systems and improved FVIII-encoding mRNA should foster the production of functional molecules and reduce their immunogenicity.

Published
2020

14. A Role for Exposed Mannosylations in Presentation of Human Therapeutic Self-Proteins to CD4+ T Lymphocytes

Author

Dasgupta, Suryasarathi, Navarrete, Ana-Maria, Bayry, Jagadeesh, Delignat, Sandrine, Wootla, Bharath, André, Sébastien, Christophe, Olivier, Nascimbeni, Michelina, Jacquemin, Marc, Martinez-Pomares, Luisa, Geijtenbeek, Teunis B. H., Moris, Arnaud, Saint-Remy, Jean-Marie, Kazatchkine, Michel D., Kaveri, Srinivas V., and Lacroix-Desmazes, Sébastien

Published
2007
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20. Intravenous immunoglobulin and dendritic cells

Author

Misra, Namita, Bayary, Jagadeesh, Dasgupta, Sooryasarathi, Ephrem, Amal, Van Huyen, Jean-Paul Duong, Delignat, Sandrine, Hassan, Gazzala, Caligiuri, Giuseppina, Nicoletti, Antonino, Lacroix-Desmazes, Sebastien, Kazatchkine, Michel D., and Kaveri, Srini V.

Published
2005
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29. Acquired Hemophilia A in IgG4-Related Disease: Case Report, Immunopathogenic Study, and Review of the Literature

Author

Sanges, Sébastien, primary, Jeanpierre, Emmanuelle, additional, Lopez, Benjamin, additional, Russick, Jules, additional, Delignat, Sandrine, additional, Carpentier, Benjamin, additional, Dubois, Romain, additional, Dubucquoi, Sylvain, additional, Guerrier, Thomas, additional, Hachulla, Éric, additional, Hatron, Pierre-Yves, additional, Paris, Camille, additional, Susen, Sophie, additional, Launay, David, additional, Lacroix-Desmazes, Sébastien, additional, and Terriou, Louis, additional

Published
2020
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34. Correction of bleeding in experimental severe hemophilia A by systemic delivery of factor VIII- encoding mRNA Short title: mRNA-based therapy for hemophilia A Scientific category: Thrombosis and Hemostasis

Author

Russick, Jules, Delignat, Sandrine, Milanov, Peter, Christophe, Olivier, Boros, Gábor, Denis, Cecile, Lenting, Peter, Kaveri, Srinivas, Lacroix-Desmazes, Sébastien, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hémostase et biologie vasculaire, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Lacroix-Desmazes, Sébastien

Subjects
[SDV.IMM] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

35. Prevention of the anti-factor VIII memory B-cell response by inhibition of Bruton tyrosine kinase in experimental hemophilia A

Author

Delignat, Sandrine, Russick, Jules, Gangadharan, Bagirath, Rayes, Julie, Ing, Mathieu, Voorberg, Jan, Kaveri, Srinivas V., Lacroix-Desmazes, S. bastien, Experimental Vascular Medicine, AII - Inflammatory diseases, Landsteiner Laboratory, and ACS - Microcirculation

Subjects
hemic and lymphatic diseases
Abstract

Hemophilia A is a rare hemorrhagic disorder caused by the lack of functional pro-coagulant factor VIII. Factor VIII replacement therapy in patients with severe hemophilia A results in the development of inhibitory anti-factor VIII IgG in up to 30% of cases. To date, immune tolerance induction, with daily injection of large amounts of factor VIII, is the only strategy to eradicate factor VIII inhibitors. This strategy is, however, efficient in only 60-80% of patients. We investigated whether blocking B-cell receptor signaling upon inhibition of Bruton tyrosine kinase prevents anti-factor VIII immune responses in a mouse model of severe hemophilia A. Factor VIII-naïve and factor VIII-sensitized factor VIII-deficient mice were fed with the selective inhibitor of Bruton tyrosine kinase, (R)-5-amino-1-(1-cyanopiperidin-3-yl)-3-(4-[2,4-difluorophenoxyl] phenyl)-1H pyrazole-4-carboxamide (PF-06250112), to inhibit B-cell receptor signaling prior to challenge with exogenous factor VIII. The consequences on the anti-factor VIII immune response were studied. Inhibition of Bruton tyrosine kinase during the primary anti-factor VIII immune response in factor VIII-naïve mice did not prevent the development of inhibitory anti-factor VIII IgG. In contrast, the anti-factor VIII memory B-cell response was consistently reduced upon treatment of factor VIII-sensitized mice with the Bruton tyrosine kinase inhibitor. The Bruton tyrosine kinase inhibitor reduced the differentiation of memory B cells ex vivo and in vivo following adoptive transfer to factor VIII-naïve animals. Taken together, our data identify inhibition of Bruton tyrosine kinase using PF-06250112 as a strategy to limit the reactivation of factor VIII-specific memory B cells upon re-challenge with therapeutic factor VIII.

Published
2019

41. Enzymatically oxidized phospholipids restore thrombin generation in coagulation factor deficiencies

Author

Slatter, David A., Percy, Charles L., Allen-Redpath, Keith, Gajsiewicz, Joshua M., Brooks, Nick J., Clayton, Aled, Tyrrell, Victoria J., Rosas, Marcela, Lauder, Sarah N., Watson, Andrew, Dul, Maria, Garcia-Diaz, Yoel, Aldrovandi, Maceler, Heurich, Meike, Hall, Judith, Morrissey, James H., Lacroix-Desmazes, Sebastien, Delignat, Sandrine, Jenkins, P. Vincent, Collins, Peter W., O'Donnell, Valerie B., Department of Oncology - Pathology, Cancer Center Karolinska [Karolinska Institutet] (CCK), Karolinska Institutet [Stockholm]-Karolinska Institutet [Stockholm], NASA Ames Research Center (ARC), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Cardiac Medicine, National Heart and Lung Institute, Imperial College London, École pratique des hautes études (EPHE), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)

Subjects
Adult, Blood Platelets, Male, Lipoproteins, Hemorrhage, Factor VIIa, Hemophilia A, Thromboplastin, Factor IX, Mice, Hydroxyeicosatetraenoic Acids, Animals, Humans, Blood Coagulation, Phospholipids, Aged, Aged, 80 and over, Hemostasis, Cardiopulmonary Bypass, Factor VIII, Thrombin, Middle Aged, Surface Plasmon Resonance, Blood Coagulation Factors, Neoplasm Proteins, Mice, Inbred C57BL, Cysteine Endopeptidases, Factor X, [SDV.IMM]Life Sciences [q-bio]/Immunology, lipids (amino acids, peptides, and proteins), Carrier Proteins, Research Article, circulatory and respiratory physiology
Abstract

International audience; Hemostatic defects are treated using coagulation factors; however, clot formation also requires a procoagulant phospholipid (PL) surface. Here, we show that innate immune cell-derived enzymatically oxidized phospholipids (eoxPL) termed hydroxyeicosatetraenoic acid-phospholipids (HETE-PLs) restore hemostasis in human and murine conditions of pathological bleeding. HETE-PLs abolished blood loss in murine hemophilia A and enhanced coagulation in factor VIII-(FVIII-), FIX-, and FX-deficient human plasma. HETE-PLs were decreased in platelets from patients after cardiopulmonary bypass (CPB). To explore molecular mechanisms, the ability of eoxPL to stimulate individual isolated coagulation factor/cofactor complexes was tested in vitro. Extrinsic tenase (FVIIa/tissue factor [TF]), intrinsic tenase (FVIIIa/FIXa), and prothrombinase (FVa/FXa) all were enhanced by both HETE-PEs and HETE-PCs, suggesting a common mechanism involving the fatty acid moiety. In plasma, 9-, 15-, and 12-HETE-PLs were more effective than 5-, 11-, or 8-HETE-PLs, indicating positional isomer specificity. Coagulation was enhanced at lower lipid/factor ratios, consistent with a more concentrated area for protein binding. Surface plasmon resonance confirmed binding of FII and FX to HETE-PEs. HETE-PEs increased membrane curvature and thickness, but not surface charge or homogeneity, possibly suggesting increased accessibility to cations/factors. In summary, innate immune-derived eoxPL enhance calcium-dependent coagulation factor function, and their potential utility in bleeding disorders is proposed.

Published
2018
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43. Induction of maturation and activation of human dendritic cells: A mechanism underlying the beneficial effect of Viscum album as complimentary therapy in cancer

Author

Delignat Sandrine, van Huyen Jean-Paul, Elluru Sri, Kazatchkine Michel D, Friboulet Alain, Kaveri Srini V, and Bayry Jagadeesh

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Viscum album (VA) preparations have been used as a complimentary therapy in cancer. In addition to their cytotoxic properties, they have also been shown to have immunostimulatory properties. In the present study, we examine the hypothesis that the VA preparations induce activation of human DC that facilitates effective tumor regression. Methods Four day old monocyte-derived immature DCs were treated with VA Qu Spez at 5, 10 and 15 μg/ml for 48 hrs. The expression of surface molecules was analyzed by flow cytometry. The ability of Qu Spez-educated DC to stimulate T cells was analyzed by allogeneic mixed lymphocyte reaction and activation of Melan-A/MART-1-specific M77-80 CD8+T cells. Cytokines in cell free culture supernatant was analyzed by cytokine bead array assay. Results VA Qu Spez stimulated DCs presented with increased expression of antigen presenting molecule HLA-DR and of co-stimulatory molecules CD40, CD80 and CD86. The VA Qu Spez also induced the secretion of inflammatory cytokines IL-6 and IL-8. Further, Qu Spez-educated DC stimulated CD4+T cells in a allogeneic mixed lymphocyte reaction and activated melanoma antigen Melan-A/MART-1-specific M77-80 CD8+T cells as evidenced by increased secretion of TNF-α and IFNγ. Conclusion The VA preparations stimulate the maturation and activation of human DCs, which may facilitate anti-tumoral immune responses. These results should assist in understanding the immunostimulatory properties of VA preparations and improving the therapeutic strategies.

Published
2008
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44. Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the société Francophone de greffe de moelle et de thérapie cellulaire (SFGM-TC)

Author

Gilardin, Laurent, Delignat, Sandrine, Peyron, Ivan, Ing, Mathieu, Lone, Yu-Chun, Gangadharan, Bagirath, Michard, Baptiste, Kherabi, Yousra, Sharma, Meenu, Pashov, Anastas, Toutirais, Olivier, Loiseau, Pascale, Veyradier, Agnès, Kaveri, Srini, Maillere, Bernard, Coppo, Paul, Lacroix-Desmazes, Sébastien, Chatillon, Jean-François, Hamieh, Mohamad, Bayeux, Florence, Abasq, Claire, Fauquembergue, Emilie, Drouet, Aurélie, Guisier, Florian, Latouche, Jean-Baptiste, Musette, Philippe, Coignard-Biehler, Hélène, Mahlaoui, Nizar, Pilmis, Benoit, Barlogis, Vincent, Brosselin, Pauline, de Vergnes, Nathalie, Debré, Marianne, Malphettes, Marion, Frange, Pierre, Catherinot, Emilie, Pellier, Isabelle, Durieu, Isabelle, Perlat, Antoinette, Royer, Bruno, Le Quellec, Alain, Jeziorski, Eric, Fischer, Alain, Lortholary, Olivier, Aaron+, Laurent, Adoue, Daniel, Aguilar, Claire, Aladjidi, Nathalie, Alcaïs, Alexandre, Amoura, Zahir, Arlet, Philippe, Armari-Alla, Corinne, Bader-Meunier, Brigitte, Bayart, Sophie, Bienvenu, Boris, Blanche, Stéphane, Bodet, Damien, Bonnotte, Bernard, Borie, Raphael, Boutard, Patrick, Briandet, Claire, Brion, Jean-Paul, Brouard, Jacques, Cohen-Beaussant, Sarah, Costes, Laurence, Couderc, Louis-Jean, Cougoul, Pierre, Courteille, Virginie, de Saint Basile, Geneviève, Devoldere, Catherine, Deville, Anne, Donadieu, Jean, Doré, Eric, Dulieu, Fabienne, Edan, Christine, Entz-Werlé, Natacha, Fieschi, Claire, Forestier, Amandine, Fouyssac, Fanny, Gajdos, Vincent, Galicier, Lionel, Gandemer, Virginie, Gardembas, Martine, Gaud, Catherine, Guillerm, Gaelle, Hachulla, Eric, Hamidou, Mohamed, Hermine, Olivier, Hoarau, Cyrille, Humbert, Sebastien, Jaccard, Arnaud, Jacquot, Serge, Jais, Jean-Philippe, Jaussaud, Roland, Jeandel, Pierre-Yves, Kebaili, Kamila, Korganow, Anne-Sophie, Lambotte, Olivier, Lanternier, Fanny, Larroche, Claire, Lascaux, Anne-Sophie, Le Moigne, Emmanuelle, Le Moing, Vincent, Lebranchu, Yvon, Lecuit, Marc, Lefèvre, Guillaume, Lemal, Richard, Te, Valérie Li Thiao, Marie-Cardine, Aude, Silva, Nicolas Martin, Masseau, Agathe, Massot, Christian, Mazingue, Françoise, Merlin, Etienne, Monlibert, Béatrice, Monpoux, Fabrice, Moshous, Despina, Mouthon, Luc, Munzer, Martine, Neven, Bénédicte, Nove-Josserand, Raphaëlle, Oksenhendler, Eric, Ouachée-Chardin, Marie, Oudot, Caroline, Pagnier, Anne, Pasquali, Jean-Louis, Pasquet, Marlène, Perel, Yves, Picard, Capucine, Piguet, Christophe, Plantaz, Dominique, Provot, Johan, Quartier, Pierre, Rieux-Laucat, Frédéric, Roger, Pierre-Marie, Rohrlich, Pierre-Simon, Rubié, Hervé, Salle, Valéry, Sarrot-Reynauld, Françoise, Servettaz, Amélie, Stephan, Jean-Louis, Schleinitz, Nicolas, Suarez, Felipe, Swiader, Laure, Taque, Sophie, Thomas, Caroline, Tournilhac, Olivier, Thumerelle, Caroline, Tron, François, Viallard, Jean-François, Roux, Clément, Tifratene, K, Socie, G., Galambrun, C., Bertrand, Yves, Rialland, F., Jubert, C, Pochon, C, Paillard, C., Sirvent, A., Nelken, B., Vannier, Jean-Pierre, Freycon, C, Beguin, Y, Raus, N, Yakoub-Agha, I., Mohty, M., Dalle, J-H, Michel, Gérard, Pradier, C., Peffault de Latour, R., Rohrlich, P-S, Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Greffes d'Epitheliums et Regulation de l'Activation Lymphocytaire, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Institut Stephan Angeloff, Réseau International des Instituts Pasteur (RIIP), Immunogénétique humaine, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hématologie Biologique [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Département d'Ingénierie et d'Etudes des Protéines, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Génétique du cancer et des maladies neuropsychiatriques (GMFC), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'immuno-hématologie pédiatrique [CHU Necker], Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Unité d'Immunologie Hématologie et Rhumatologie Pédiatrique [Necker, Paris], Hôpital Foch [Suresnes], Innate Immunity and Immunotherapy (CRCINA-ÉQUIPE 7), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne - Centre Hospitalier Lyon Sud, Hospices Civils de Lyon (HCL)-Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], CHU Amiens-Picardie, Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Département de Pédiatrie et maladies infectieuses [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service Médecine Interne et immunologie clinique [CHU Toulouse], Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital de la Tronche, Département d'Immunologie, hématologie et rhumatologie pédiatriques [Hôpital Necker-Enfants malades - APHP], Hématogoie pédiatrique, hôpital Sud, Laboratoire de Mathématiques Nicolas Oresme (LMNO), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service des Maladies Infectieuses, CHU Grenoble, Service de Pédiatrie Médicale [Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Hémato-oncologie Pédiatrique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Trousseau [APHP], Centre d'Investigation Clinique [CHU Clermont-Ferrand] (CIC 1405), Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Département d'Oncologie Pédiatrique [CHU Hautepierre, Strasbourg], Hôpital de Hautepierre [Strasbourg], Immunologie clinique [CHU St-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie et d'Oncologie Pédiatrique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine de l'enfant et de l'adolescent [CHU Rennes], Apoptosis and Tumor Progression (CRCINA-ÉQUIPE 9), Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours (UT), Ecole Polytechnique Fédérale de Lausanne (EPFL), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Service d'informatique médicale et biostatistiques [CHU Necker], Université de Reims Champagne-Ardenne (URCA), Institut d’Hémato-Oncologie Pédiatrique, Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), service de Médecine Interne et d'Immunologie Clinique [AP-HP Hôpital Bicêtre], Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris (AP-HP), Internal Medicine, Paris, Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Catalysis, Synthesis of Biomolecules and Sustainable Development (CSB2D), Centre National de la Recherche Scientifique (CNRS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Unité de Biostatistique et de Recherche Clinique (UBRC), Dept of Physiology, McGill University = Université McGill [Montréal, Canada], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut Jean Godinot [Reims], UNICANCER, Service d'Immunopathologie Clinique, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service Immuno Hémato-Onco Pédiatrique, Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service Hématologie Infantile, Immunogenetics of pediatric autoimmune diseases (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Département de Médecine Interne, Immunologie clinique et maladies infectieuses [CHU Reims], Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'Hématologie et d'Oncologie pédiatrique, Service d'hématologie clinique, Hôpital Hôtel-Dieu [Paris], Service de pneumologie pédiatrique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Protéines de défense des réponses immune et inflammatoire : identification, régulation et rôles physiopathologiques, Médecine Interne, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Pediatrie Debrousse, Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Institut de Combustion, Aérothermique, Réactivité et Environnement (ICARE), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Institut des Sciences de l'Ingénierie et des Systèmes (INSIS - CNRS), Service d'Hématologie et d'Oncologie Médicale, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Service d'hémato-immuno-oncologie pédiatrique [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Etablissement français du sang [Poitiers] (EFS), Public Health Department, Hôpital de l'Archet, Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), École pratique des hautes études (EPHE)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Antoine Béclère, Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Innate immunity and Immunotherapy (CRCINA - Département INCIT - Equipe 7), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de médecine interne, Hôpital Universitaire d'Amiens, CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Service de médecine interne, hôpital Purpan, Hôpital Sud, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Service d’oncologie hématologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], CIC - Clermont Ferrand, Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine de l'enfant et de l'adolescent, CHU Pontchaillou [Rennes]-Hôpital Sud, Apoptose et Progression tumorale (CRCNA / Equipe 9), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche en Santé de l'Université de Nantes (IRS-UN), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Lille Inflammation Research International Center (LIRIC), Université de Tours, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Recherches Translationnelles sur le VIH et les maladies infectieuses (TransVIHMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Université Montpellier 1 (UM1)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Universtié Yaoundé 1 [Cameroun]-Université de Montpellier (UM), CHU Toulouse [Toulouse]-Hôpital de Rangueil, Institute of Chemistry for Life and Health Sciences (i-CLEHS), Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias - Clermont Auvergne (CHELTER), Université Clermont Auvergne (UCA), McGill University, Institut Jean Godinot, CRLCC Jean Godinot, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hématologie pédiatrique, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA), Unité d'Hémato-Oncologie, Hôpital des Enfants, CHU Saint-Etienne, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Institut des Sciences de l'Ingénierie et des Systèmes (INSIS), CHU Saint-Antoine [APHP], École pratique des hautes études (EPHE), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Chaire Médecine expérimentale (A. Fischer), Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Pontchaillou [Rennes]-hôpital Sud, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)

Subjects
Oncology, medicine.medical_specialty, Palliative care, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hematopoietic stem cell transplantation, Donor lymphocyte infusion, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Transplantation, Homologous, Treatment Failure, Child, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Transplantation, Acute leukemia, Chemotherapy, Leukemia, business.industry, Palliative Care, Hematopoietic Stem Cell Transplantation, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, medicine.disease, Donor Lymphocytes, Leukemia, Biphenotypic, Acute, 3. Good health, Surgery, Survival Rate, Leukemia, Myeloid, Acute, Treatment Outcome, Lymphocyte Transfusion, 030220 oncology & carcinogenesis, Acute Disease, Disease Progression, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, 030215 immunology
Abstract

Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in the case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent 10-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted of chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and donor lymphocyte infusion (DLI; n=30), or isolated reinfusion of donor lymphocytes (DLI; n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy=385 days, second allograft=391 days, chemotherapy=174 days, DLI alone=140 days, palliative care=43 days. A second SCT or a combination of chemotherapy and DLI yielded similar outcome (hazard ratio (HR)=0.85, P=0.53) unlike chemotherapy alone (HR=1.43 P=0.04), palliative care (HR=4.24, P

Published
2017
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46. Removal of Mannose-Ending Glycan at Asn2118 Abrogates FVIII Presentation by Human Monocyte-Derived Dendritic Cells.

Author

Delignat, Sandrine, Rayes, Julie, Dasgupta, Suryasarathi, Gangadharan, Bagirath, Denis, Cécile V., Christophe, Olivier D., Bayry, Jagadeesh, Kaveri, Srinivas V., and Lacroix-Desmazes, Sébastien

Subjects
DENDRITIC cells, T cells, CELL receptors, ANIMAL models in research, GENETIC transformation
Abstract

The development of an immune response against therapeutic factor VIII is the major complication in hemophilia A patients. Oligomannose carbohydrates at N239 and/or N2118 on factor VIII allow its binding to the macrophage mannose receptor expressed on human dendritic cells, thereby leading to factor VIII endocytosis and presentation to CD4+ T lymphocytes. Here, we investigated whether altering the interaction of factor VIII with mannose-sensitive receptors on antigen-presenting cells may be a strategy to reduce factor VIII immunogenicity. Gene transfer experiments in factor VIII-deficient mice indicated that N239Q and/or N2118Q factor VIII mutants have similar specific activities as compared to non-mutated factor VIII; N239Q/N2118Q mutant corrected blood loss upon tail clip. Production of the corresponding recombinant FVIII mutants or light chains indicated that removal of the N-linked glycosylation site at N2118 is sufficient to abrogate in vitro the activation of FVIII-specific CD4+ T cells by human monocyte-derived dendritic cells. However, removal of mannose-ending glycans at N2118 did not alter factor VIII endocytosis and presentation to CD4+ T cells by mouse antigen-presenting cells. In agreement with this, the N2118Q mutation did not reduce factor VIII immunogenicity in factor VIII-deficient mice. Our results highlight differences in the endocytic pathways between human and mouse dendritic cell subsets, and dissimilarities in tissue distribution and function of endocytic receptors such as CD206 in both species. Further investigations in preclinical models of hemophilia A closer to humans are needed to decipher the exact role of mannose-ending glycans in factor VIII immunogenicity. [ABSTRACT FROM AUTHOR]

Published
2020
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49. Complement C3 is a novel modulator of the anti-factor VIII immune response

Author

Rayes, Julie, primary, Ing, Mathieu, additional, Delignat, Sandrine, additional, Peyron, Ivan, additional, Gilardin, Laurent, additional, Vogel, Carl-Wilhelm, additional, Fritzinger, David C., additional, Frémeaux-Bacchi, Véronique, additional, Kaveri, Srinivas V., additional, Roumenina, Lubka T., additional, and Lacroix-Desmazes, Sébastien, additional

Published
2017
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50. The ADAMTS13 1239–1253 peptide is a dominant HLA-DR1-restricted CD4 + T-cell epitope

Author

Gilardin, Laurent, primary, Delignat, Sandrine, additional, Peyron, Ivan, additional, Ing, Mathieu, additional, Lone, Yu-Chun, additional, Gangadharan, Bagirath, additional, Michard, Baptiste, additional, Kherabi, Yousra, additional, Sharma, Meenu, additional, Pashov, Anastas, additional, Latouche, Jean-Baptiste, additional, Hamieh, Mohamad, additional, Toutirais, Olivier, additional, Loiseau, Pascale, additional, Galicier, Lionel, additional, Veyradier, Agnès, additional, Kaveri, Srini, additional, Maillère, Bernard, additional, Coppo, Paul, additional, and Lacroix-Desmazes, Sébastien, additional

Published
2017
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