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1. Rituximab therapy for childhood Evans syndrome

Author: Brigitte Bader-Meunier, Nathalie Aladjidi, Françoise Bellmann, Fabrice Monpoux, Brigitte Nelken, Alain Robert, Corinne Armari-Alla, Capucine Picard, Françoise Ledeist, Martine Munzer, Karima Yacouben, Yves Bertrand, Antoine Pariente, Arnaud Chaussé, Yves Perel, and Guy Leverger
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: The safety and efficacy of rituximab have been retrospectively assessed in 17 children with Evans syndrome. Patients received 4 or 3 weekly doses of rituximab (375 mg/m2 per dose) associated with prednisone, alone (14 patients) or associated with other immunosuppressive drugs. Complete or partial remission of at least one cytopenia was achieved in 13 out of the 17 patients (76%), and lasted in 11 of them with a mean follow-up of 2.4 years (range 0.5–7 years). Steroid therapy was stopped or tapered at 50–100% of the baseline dosage in all long-term responders. Moderate side effects and infection occurred only in 4 and 1 children respectively.
Published: 2007
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2. Changements de pratiques dans la prise en charge de l’hémophilie majeure en pédiatrie

Author: Carine Cerato-Blanc and Fabrice Monpoux
Subjects: Emicizumab, medicine.medical_specialty, business.industry, Nice, Haemophilia, medicine.disease, University hospital, Family medicine, Medicine, business, computer, health care economics and organizations, General Nursing, Experience sharing, computer.programming_language
Abstract: Recent therapeutic innovations are significantly changing the management of young children with severe haemophilia. A team from the University Hospital of Nice (06) introduced emicizumab, the first subcutaneous non-replacement therapy. Integrated into the multi-professional management of children and their families, this innovative therapeutic option has shown encouraging initial results. Experience sharing.
Published: 2021

3. [Practice changes in the management of major paediatric haemophilia]

Author: Carine, Cerato-Blanc and Fabrice, Monpoux
Subjects: Child, Preschool, Humans, Child, Hemophilia A
Abstract: Recent therapeutic innovations are significantly changing the management of young children with severe haemophilia. A team from the University Hospital of Nice (06) introduced emicizumab, the first subcutaneous non-replacement therapy. Integrated into the multi-professional management of children and their families, this innovative therapeutic option has shown encouraging initial results. Experience sharing.
Published: 2021

4. Tolerance induction to deferasirox in a child with transfusion-dependent beta thalassemia

Author: Fanny Rocher, Carole Bailly-Piccini, Morgane Pondrom, Fabrice Monpoux, Nadia Gastaut, and Maryline Poirée
Subjects: Pediatrics, medicine.medical_specialty, Thalassemia, Iron Chelating Agents, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, hemic and lymphatic diseases, 030225 pediatrics, Immune Tolerance, medicine, Humans, Iron Chelator, business.industry, beta-Thalassemia, Deferasirox, Infant, Beta thalassemia, medicine.disease, Deferoxamine, Tolerance induction, chemistry, Desensitization, Immunologic, Child, Preschool, Pediatrics, Perinatology and Child Health, Transfusion dependence, Drug Eruptions, Deferiprone, business, medicine.drug
Abstract: Beta thalassemias are autosomal recessive hemoglobin disorders related to a defect in the beta-globin chain production. Most of the major forms of beta-thalassemia are transfusion dependent leading to iron overload. Today, three iron chelators are available in France. We report the case of a patient suffering from β+ major transfusion-dependent thalassemia who presented with severe skin reactions to deferoxamine and deferasirox as well as with agranulocytosis after deferiprone administration. The patient benefited from successful tolerance induction to deferasirox. With the increasing number of children suffering from iron overload, we believe that our protocol can be useful to pediatric hematology teams confronted with multiple iron chelator reactions.
Published: 2021

5. An appraisal of the frequency and severity of noninfectious manifestations in primary immunodeficiencies: A study of a national retrospective cohort of 1375 patients over 10 years

Author: Mickaël Alligon, Nizar Mahlaoui, Virginie Courteille, Laurence Costes, Veronica Afonso, Philippe Randrianomenjanahary, Nathalie de Vergnes, Anja Ranohavimparany, Duy Vo, Inès Hafsa, Perrine Bach, Vincent Benoit, Nicolas Garcelon, Alain Fischer, Wadih Abou-Chahla, Daniel Adoue, Nathalie Aladjidi, Corinne Armari-Alla, Vincent Barlogis, Sophie Bayart, Yves Bertrand, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, David Boutboul, Claire Briandet, Jean-Paul Brion, Jacques Brouard, Liana Carausu, Martin Castelle, Pascal Cathebras, Emilie Catherinot, Nathalie Cheikh, Morgane Cheminant, Sarah Cohen-Beaussant, Thibault Comont, Louis-Jean Couderc, Pierre Cougoul, Gérard Couillault, Lionel Crevon, Elisa Demonchy, Anne Deville, Catherine Devoldere, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Natacha Entz-Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Aurélien Guffroy, Corinne Guitton, Gaëlle Guillerm, Eric Hachulla, Mohamed Hamidou, Sophie Haro, Yves Hatchuel, Olivier Hermine, Cyrille Hoarau, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Jean-Philippe Jais, Sarah Jannier, Serge Jacquot, Roland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Olivier Lambotte, Fanny Lanternier, Claire Larroche, David Launay, Emmanuelle Le Moigne, Alain Le Quellec, Vincent Le Moing, Yvon Lebranchu, Marc Lecuit, Guillaume Lefèvre, Jean-Daniel Lelièvre, Richard Lemal, Valérie Li-Thiao-Te, Olivier Lortholary, Luminita Luca, Coralie Mallebranche, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin-Silva, Agathe Masseau, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Charline Miot, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Münzer, Robert Navarro, Bénédicte Neven, Dalila Nouar, Raphaële Nove-Josserand, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Christophe Piguet, Dominique Plantaz, Sophie Rivière, Pascal Roblot, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Harry Sokol, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, and Jean-François Viallard
Subjects: Inflammation, Neoplasms, Immunology, Hypersensitivity, Immunologic Deficiency Syndromes, Immunology and Allergy, Humans, Autoimmunity, Retrospective Studies
Abstract: Noninfectious manifestations-allergy, autoimmunity/inflammation, lymphoproliferation, and malignancies-are known to exist in many primary immunodeficiency diseases (PID) and to participate in prognosis.To obtain a global view on their occurrence, we retrieved data from a retrospective cohort of 1375 patients included in the French National Reference Center for Primary Immune Deficiencies (CEREDIH) for whom we had a 10-year follow-up since inclusion in the registry.These patients were followed for 10 years (2009-2018) by specialized centers in university hospitals. This study showed that 20.1% of patients without prior curative therapy (n = 1163) developed at least 1 manifestation (event) encompassing 277 events.Autoimmune/inflammatory events (n = 138) and malignancies (n = 85) affected all age classes and virtually all PID diagnostic groups. They were associated with a risk of death that occurred in 195 patients (14.2%) and were found to be causal in 43% of cases. Malignancies (odds ratio, 5.62; 95% confidence interval, 3.66-8.62) and autoimmunity (odds ratio, 1.9; 95% confidence interval, 1.27-2.84) were clearly identified as risk factors for lethality. Patients who underwent curative therapy (mostly allogeneic hematopoietic stem cell transplantation, with a few cases of gene therapy or thymus transplantation) before the 10-year study period (n = 212) had comparatively reduced but still detectable clinical manifestations (n = 16) leading to death in 9.4% of them.This study points to the frequency and severity of noninfectious manifestations in various PID groups across all age groups. These results warrant further prospective analysis to better assess their consequences and to adapt therapy, notably indication of curative therapy.
Published: 2021

6. Long-term outcomes of lentiviral gene therapy for the β-hemoglobinopathies: the HGB-205 trial

Author: Elisa Magrin, Michaela Semeraro, Nicolas Hebert, Laure Joseph, Alessandra Magnani, Anne Chalumeau, Aurélie Gabrion, Cécile Roudaut, Jouda Marouene, Francois Lefrere, Jean-Sebastien Diana, Adeline Denis, Bénédicte Neven, Isabelle Funck-Brentano, Olivier Negre, Sylvain Renolleau, Valentine Brousse, Laurent Kiger, Fabien Touzot, Catherine Poirot, Philippe Bourget, Wassim El Nemer, Stéphane Blanche, Jean-Marc Tréluyer, Mohammed Asmal, Courtney Walls, Yves Beuzard, Manfred Schmidt, Salima Hacein-Bey-Abina, Vahid Asnafi, Isabelle Guichard, Maryline Poirée, Fabrice Monpoux, Philippe Touraine, Chantal Brouzes, Mariane de Montalembert, Emmanuel Payen, Emmanuelle Six, Jean-Antoine Ribeil, Annarita Miccio, Pablo Bartolucci, Philippe Leboulch, and Marina Cavazzana
Subjects: Male, Young Adult, Treatment Outcome, Adolescent, Lentivirus, beta-Thalassemia, Humans, Female, General Medicine, Anemia, Sickle Cell, Genetic Therapy, General Biochemistry, Genetics and Molecular Biology
Abstract: Sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT) are the most prevalent monogenic disorders worldwide. Trial HGB-205 ( NCT02151526 ) aimed at evaluating gene therapy by autologous CD34
Published: 2020

7. Compliance with Early Long-Term Prophylaxis Guidelines for Severe Hemophilia A

Author: Paul Saultier, Yves Guillaume, Virginie Demiguel, Claire Berger, Annie Borel-Derlon, Ségolène Claeyssens, Annie Harroche, Caroline Oudot, Anne Rafowicz, Marc Trossaert, Bénédicte Wibaut, Christine Vinciguerra, Mohamed Boucekine, Karine Baumstarck, Sandrine Meunier, Thierry Calvez, Hervé Chambost, Achille Aouba, Faezeh Legrand, Chantal Rothschild, Marie-Françoise Torchet, Roseline d’Oiron, Thierry Lambert, Yves Laurian, Jennifer Biernat, Jenny Goudemand, Armelle Parquet, Véronique Tintillier, Anne Durin Assollant, Claude Négrier, Sabine Castet, Viviane Guérin, Yohann Huguenin, Marguerite Micheau, Anne Ryman, Hérve Chambost, Céline Falaise, Marie Françoise Thiercelin-Legrand, Marianne Fiks-Sigaud, Marc Fouassier, Edith Fressinaud, Sophie Voisin, Albert Faradji, Patrick Lutz, Marie Elisabeth Briquel, Birgit Frotscher, Béatrice Fimbel, Yves Gruel, Claude Guerois, Sandra Regina, Jean Baptiste Valentin, Christine Biron Andreani, Philippe Codine, Daniel Donadio, Robert Navarro, Paola Rospide, Jean-François Schved, Bénédicte Collet, Annie Borel Derlon, Philippe Gautier, Sophie Bayart, Ben⊚ıt Guillet, JeanneYvonne Borg, Cécile Dumesnil, Charline Normand, Pascale Schneider, Philippe Tron, Jean-Pierre Vannier, Fabienne Dutrillaux, Fabienne Volot, Piotr Gembara, Alain Marques-Verdier, Dalila Adjaoud, Claire Barro, Gilles Pernod, Ben⊚ıt Polack, Patricia Pouzol, Nadra Ounnoughene, Patricia Paugy, Valérie Robert, Natalie Stieltjes, Brigitte Bastenaire, Emmanuelle de Raucourt, Jocelyne Peynet, Valérie Li-Thiao-Te, Brigitte Pautard, Catherine Behar, Stéphanie Gorde, Martine Munzer, Valérie Gay, Elisabeth Benz Lemoine, Laurent Macchi, Lionel De Lumley, Solange Gaillard, Anne Deville, Fabrice Monpoux, Marie Anne Bertrand, Brigitte Pan-Petesch, Abel Hassoun, Brigitte Coatmelec, Philippe Beurrier, Michèle Damay, Philippe Moreau, Odile Pouille-Lievin, Caroline Schoepfer, Eliane Tarral, Monique Bianchin, Joël Nguyen, Olivier Pincemaille, Marie-Odile Peter, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpitaux de Saint Maurice (HNSM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Universitaire des Maladies Rénales [CHU Caen] (CUMR Caen), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Limoges, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hospices Civils de Lyon (HCL), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), and Université de Montpellier (UM)
Subjects: Male, Pediatrics, medicine.medical_specialty, Multivariate analysis, [SDV]Life Sciences [q-bio], Population, Long term prophylaxis, Kaplan-Meier Estimate, Hemophilia A, Severe hemophilia A, Severity of Illness Index, Early initiation, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Humans, Medicine, Cumulative incidence, 030212 general & internal medicine, Practice Patterns, Physicians', education, Birth Year, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, education.field_of_study, business.industry, Infant, Newborn, Infant, Blood Coagulation Factors, Logistic Models, Child, Preschool, Practice Guidelines as Topic, Pediatrics, Perinatology and Child Health, Cohort, France, Guideline Adherence, Joint Diseases, business
Abstract: International audience; Objectives: To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline compliance.Study design: This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation).Results: We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with "timely long-term prophylaxis" as compared with "delayed long-term prophylaxis": hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with "long-term prophylaxis guideline compliance" vs "long-term prophylaxis anticipation."Conclusions: This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.
Published: 2021

8. Genetic diagnosis of primary immunodeficiencies: A survey of the French national registry

Author: Nizar Mahlaoui, Capucine Picard, Perrine Bach, Laurence Costes, Virginie Courteille, Anja Ranohavimparany, Alexandre Alcaïs, Jean-Philippe Jais, Alain Fischer, Christine Bellanné-Chantelot, Jacinta Bustamante, Sylvie Chollet-Martin, Christian Drouet, Véronique Fremeaux-Bacchi, Caroline Kannengiesser, Virginie Girardin, Nathalie Lambert, Valérie Proulle, Jérémie Rosain, Marie José Stasia, Dominique Stoppa Lyonnet, Ioannis Theodorou, Wadih Abou-Chahla, Daniel Adoue, Nathalie Aladjidi, Zahir Amoura, Corinne Armari-Alla, Brigitte Bader-Meunier, Vincent Barlogis, Sophie Bayart, Yves Bertrand, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, Claire Briandet, Jean-Paul Brion, Jacques Brouard, Liana Carausu, Emilie Catherinot, Nathalie Cheikh, Sarah Cohen-Beaussant, Louis-Jean Couderc, Pierre Cougoul, Gérard Couillault, Geneviève de Saint Basile, Catherine Devoldere, Anne Deville, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Natacha Entz Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Aurélien Guffroy, Corinne Guitton, Gaelle Guillerm, Eric Hachulla, Mohamed Hamidou, Sophie Haro, Yves Hatchuel, Olivier Hermine, Cyrille Hoarau, Bruno Hoen, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Serge Jacquot, Rolland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Olivier Lambotte, Fanny Lanternier, Claire Larroche, Alain Le Quellec, Emmanuelle Le Moigne, Vincent Le Moing, David Launay, Yvon Lebranchu, Marc Lecuit, Guillaume Lefevre, Richard Lemal, Valérie Li-Thiao-Te, Olivier Lortholary, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin Silva, Agathe Masseau, Christian Massot, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Munzer, Bénédicte Neven, Raphaëlle Nove-Josserand, Dalila Nouar, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Christophe Piguet, Dominique Plantaz, Pierre Quartier, Frédéric Rieux-Laucat, Pascal Roblot, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, Jean-François Viallard, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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, Service de Biostatistique et Informatique Médicale, Université Paris Descartes - Paris 5 (UPD5), Service d'immuno-hématologie pédiatrique [CHU Necker], Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Immunologie 'Autoimmunité et Hypersensibilités' [AP-HP Hôpital Bichat, Paris], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe de Recherche et d'Etude du Processus Inflammatoire (GREPI), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'immunologie [HEGP, Paris], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), the Study Center of Primary Immunodeficiencies, CHU Necker - Enfants Malades [AP-HP], Hémostase et biologie vasculaire, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre d'Immunologie et de Maladies Infectieuses (CIMI), 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), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôpital de la Tronche, Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hématogoie pédiatrique, hôpital Sud, SIGNAL-IMAGE-COMMUNICATION (SIC), Université de Poitiers-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), Service de Pneumologie et Centre de Compétence des Maladies Pulmonaires Rares [AP-HP Hôpital Bichat, Paris], 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], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Foch [Suresnes], Service de pédiatrie (CHU de Dijon), 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), Centre Hospitalier Universitaire de Nice (CHU Nice), 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, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), 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), Infections à Vih, Réservoirs, Pharmacologie des Antirétroviraux et Prévention de la Transmission Mère Enfant, 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), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], Service d'Immunologie Clinique et de Médecine Interne, Centre National de Référence des Maladies Auto-immunes Rares, Hôpitaux Universitaires de Strasbourg, Service d'hématologie, immunologie biologiques et cytogénétique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service Hématologie, Hôpital Morvan [Brest]-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Claude Huriez [Lille], CHU Lille, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, cellules dendritiques et greffes (JE 2448), Université de Tours (UT), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Service de Médecine Interne, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), 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, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Médecine interne, maladies infectieuses, immunologie clinique, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut d’Hémato-Oncologie Pédiatrique, INSERM U1012, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Internal Medicine, Paris, 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), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département Maladies Infectieuses et Tropicales, Hôpital Universitaire, Montpellier, France, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Laboratoire de Génie Electrique de Grenoble (G2ELab), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Clermont-Ferrand, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Dept of Physiology, McGill University = Université McGill [Montréal, Canada], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], American Memorial Hospital, American Memory Hospital, Department of Clinical Immunology, 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 Immuno Hémato-Onco Pédiatrique, Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Service Hématologie Infantile, CHU Amiens-Picardie, 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), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de médecine de l'enfant et de l'adolescent [CHU Rennes], Clinical Haematology, CHU Hôtel-Dieu, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1 (UB)-CHU Bordeaux [Bordeaux], French Ministry of Health, LFB, GlaxoSmithKlineGlaxoSmithKline, CSL BehringCSL Behring, ShireShire, Octapharma, Binding Site, 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, Chaire Médecine expérimentale (A. Fischer), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), GREPI, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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]), 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), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), 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), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hématologie pédiatrique, CHU Toulouse [Toulouse], CHU Saint-Etienne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Service de médecine de l'enfant et de l'adolescent, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-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) (APHP)-CHU Necker - Enfants Malades [AP-HP], 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, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sud, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), 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), 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), Service de médecine interne, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Morvan [Brest], Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Tours, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Paris Diderot - Paris 7 (UPD7)-CHU Saint Louis [APHP], McGill University, Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Centre de Recherche sur le Cancer Nantes-Angers (LUNAM), Université d'Angers (UA)-Université de Nantes (UN), Centre Hospitalier Universitaire d'Amiens (CHU), centre hospitalier universitaire amiens, CHU Bordeaux [Bordeaux]-Université Sciences et Technologies - Bordeaux 1, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), and 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)
Subjects: 0301 basic medicine, Primary Immunodeficiency Diseases, medicine.medical_treatment, Genetic counseling, Immunology, Genomics, Bioinformatics, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Genotype, Humans, Immunology and Allergy, Medicine, Genetic Testing, Registries, Retrospective Studies, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], business.industry, Common variable immunodeficiency, Retrospective cohort study, medicine.disease, Phenotype, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Identification (biology), France, business, 030215 immunology
Abstract: International audience; To the Editor:Since the mid-1980s, continuous progress in genetics and genomics has accelerated the rapid identification of causative genetic variants leading to primary immunodeficiencies (PIDs; >300 genes),1 with the noticeable exception of B-cell disorders, such as common variable immunodeficiency (CVID). The identification of these mutations not only validates a clinical diagnosis but also is useful in several other respects (more accurate prognosis on phenotype/genotype correlation, targeted therapy, and genetic counseling). [...]
Published: 2019

9. Determinants of adherence and consequences of the transition from adolescence to adulthood among young people with severe haemophilia (TRANSHEMO): study protocol for a multicentric French national observational cross-sectional study

Author: Noémie Resseguier, Natacha Rosso-Delsemme, Any Beltran Anzola, Karine Baumstarck, Vanessa Milien, Laurent Ardillon, Sophie Bayart, Claire Berger, Marie-Anne Bertrand, Christine Biron-Andreani, Annie Borel-Derlon, Sabine Castet, Pierre Chamouni, Ségolène Claeyssens Donadel, Emmanuelle De Raucourt, Dominique Desprez, Céline Falaise, Birgit Frotscher, Valérie Gay, Jenny Goudemand, Yves Gruel, Benoît Guillet, Annie Harroche, Abel Hassoun, Yoann Huguenin, Thierry Lambert, Aurélien Lebreton, Anne Lienhart, Michèle Martin, Sandrine Meunier, Fabrice Monpoux, Guillaume Mourey, Claude Negrier, Philippe Nguyen, Placide Nyombe, Caroline Oudot, Brigitte Pan-Petesch, Benoît Polack, Anne Rafowicz, Antoine Rauch, Delphine Rivaud, Pascale Schneider, Alexandra Spiegel, Cecile Stoven, Brigitte Tardy, Marc Trossaërt, Jean-Baptiste Valentin, Stéphane Vanderbecken, Fabienne Volot, Annelise Voyer-Ebrard, Bénédicte Wibaut, Tanguy Leroy, Thomas Sannie, Hervé Chambost, Pascal Auquier, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hématogoie pédiatrique, hôpital Sud, Département d'hématologie biologique[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'Hématologie Biologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Laboratoire d'hématologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre Hospitalier de Versailles André Mignot (CHV), Service de pédiatrie, d'hématologie et d'oncologie [Hôpital de La Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d’Hématologie Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Hématologie, Centre Hospitalier Chambéry, Hôpital cardiologique, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL), 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), Centre Hospitalier Universitaire de Lyon (CHU Lyon), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Hôpital Morvan [Brest], Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), CIC Brest, Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Cavale Blanche, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service d'hémato-immuno-oncologie pédiatrique [Rouen], Groupe de recherche sur la thrombose, pharmacologie des antithrombotiques et situations à risque (GRT), Université Jean Monnet - Saint-Étienne (UJM), Centre hospitalier universitaire de Nantes (CHU Nantes), Groupe de Recherche en Psychologie Sociale (GRePS), Université Lumière - Lyon 2 (UL2), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Laboratoire de Santé Publique, Université de la Méditerranée - Aix-Marseille 2, Ministère des Affaires Sociales et de la Santé, Filière MHEMO, Université Aix-Marseille, Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), 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 de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Groupe de recherche sur la thrombose (GRT (EA 3065)), Université Jean Monnet [Saint-Étienne] (UJM), Hôpital Sud, Centre hospitalier de Versailles André-Mignot, 177, rue de Versailles, 78150 Le Chesnay, France, parent, Université de Tours, Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), CHU de Nancy - Hôpitaux de Brabois, 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), Université de Brest (UBO), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), 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), and Jonchère, Laurent
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Male, Activities of daily living, Cross-sectional study, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, 0302 clinical medicine, Risk Factors, Academic Performance, Protocol, Early childhood, adherence, adolescents, Young adult, ComputingMilieux_MISCELLANEOUS, Qualitative Research, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, transition, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], Patient Satisfaction, Female, Family Relations, France, Psychosocial, Attitude to Health, Haematology (Incl Blood Transfusion), Adult, young adults, medicine.medical_specialty, Transition to Adult Care, Adolescent, haemophilia, Haemophilia, Hemophilia A, 03 medical and health sciences, Young Adult, Quality of life (healthcare), 030225 pediatrics, medicine, Humans, business.industry, Protective Factors, medicine.disease, Treatment Adherence and Compliance, Cross-Sectional Studies, Social Class, Family medicine, Quality of Life, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IntroductionSevere haemophilia is a rare disease characterised by spontaneous bleeding from early childhood, which may lead to various complications, especially in joints. It is nowadays possible to avoid these complications thanks to substitutive therapies for which the issue of adherence is major. The transition from adolescence to adulthood in young people with severe haemophilia is a critical period as it is associated with a high risk of lack of adherence to healthcare, which might have serious consequences on daily activities and on quality of life.Methods and analysisWe present the protocol for a cross-sectional, observational, multicentric study to assess the differences between adolescents and young adults with severe haemophilia in France through the transition process, especially on adherence to healthcare. This study is based on a mixed methods design, with two complementary and consecutive phases, comparing data from a group of adolescents (aged 14–17 years) with those from a group of young adults (aged 20–29 years). The quantitative phase focuses on the determinants (medical, organisational, sociodemographic and social and psychosocial and behavioural factors) of adherence to healthcare (considered as a marker of the success of transition). The qualitative phase explores participants’ views in more depth to explain and refine the results from the quantitative phase. Eligible patients are contacted by the various Haemophilia Treatment Centres participating in the French national registry FranceCoag.Ethics and disseminationThe study was approved by the French Ethics Committee and by the French National Agency for Medicines and Health Products Safety (number: 2016-A01034-47). Study findings will be disseminated to the scientific and medical community in peer-reviewed journals and presented at scientific meetings. Results will be popularised to be communicated via the French association for people with haemophilia to participants and to the general public.Trial registration numberNCT02866526; Pre-results.
Published: 2018

10. Gene Therapy in Patients with Transfusion-Dependent beta-Thalassemia

Author: Stany Chrétien, Jean-Sebastien Diana, Mariane de Montalembert, Olivier Hermine, Alexandria Petrusich, Janet L. Kwiatkowski, Catherine Poirot, Sandeep Soni, Christof von Kalle, Felipe Suarez, Laure Caccavelli, David Davidson, Olivier Negre, Thibaud Lefebvre, Emmanuel Payen, Elliott Vichinsky, David T. Teachey, Philippe Leboulch, Jean-Antoine Ribeil, Marina Cavazzana, Fabrice Monpoux, Suradej Hongeng, Gabor Istvan Veres, Mark C. Walters, John E.J. Rasko, Despina Moshous, Philippe Bourget, Michaela Semeraro, Stéphane Blanche, Salima Hacein-Bey-Abina, Alessandra Magnani, Chantal Brouzes, François Lefrère, Corinne Pondarré, Jean-François Meritet, P. Joy Ho, Laura Sandler, Robert W. Ross, Mohammed Asmal, Alexis A. Thompson, Morris Kletzel, Valentine Brousse, Yves Beuzard, Hervé Puy, Usanarat Anurathapan, Elisa Magrin, Gary J. Schiller, Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)
Subjects: 0301 basic medicine, Oncology, Male, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Genetic enhancement, Thalassemia, Antigens, CD34, beta-Globins, Medical and Health Sciences, DISEASE, Hemoglobins, Stem Cell Research - Nonembryonic - Human, Child, biology, Cooley's Anemia, Gene Transfer Techniques, General Medicine, Gene Therapy, Hematology, 3. Good health, Blood, Lentivirus, LentiGlobin BB305, Stem Cell Research - Nonembryonic - Non-Human, Female, Development of treatments and therapeutic interventions, Erythrocyte Transfusion, BURDEN, Autologous, medicine.drug, Biotechnology, Adult, medicine.medical_specialty, Adolescent, Genetic Vectors, VECTOR, Transplantation, Autologous, GLOBIN GENE, 03 medical and health sciences, Young Adult, Rare Diseases, CONDITIONING REGIMEN, Clinical Research, Internal medicine, General & Internal Medicine, medicine, Genetics, Humans, Antigens, Adverse effect, Transplantation, 5.2 Cellular and gene therapies, business.industry, beta-Thalassemia, STEM-CELL TRANSPLANTATION, Genetic Therapy, biology.organism_classification, medicine.disease, Stem Cell Research, EFFICACY, BONE-MARROW-TRANSPLANTATION, HEMOGLOBINOPATHIES, 030104 developmental biology, Mutation, CD34, ERYTHROPOIESIS, business, Busulfan, Ex vivo
Abstract: International audience; BACKGROUND Donor availability and transplantation-related risks limit the broad use of allogeneic hematopoietic-cell transplantation in patients with transfusion-dependent beta-thalassemia. After previously establishing that lentiviral transfer of a marked beta-globin (beta(A-T87Q)) gene could substitute for long-term red-cell transfusions in a patient with beta-thalassemia, we wanted to evaluate the safety and efficacy of such gene therapy in patients with transfusion-dependent beta-thalassemia. METHODS In two phase 1-2 studies, we obtained mobilized autologous CD34+ cells from 22 patients (12 to 35 years of age) with transfusion-dependent beta-thalassemia and transduced the cells ex vivo with LentiGlobin BB305 vector, which encodes adult hemoglobin (HbA) with a T87Q amino acid substitution (HbA(T87Q)). The cells were then reinfused after the patients had undergone myeloablative busulfan conditioning. We subsequently monitored adverse events, vector integration, and levels of replication-competent lentivirus. Efficacy assessments included levels of total hemoglobin and HbA(T87Q), transfusion requirements, and average vector copy number. RESULTS At a median of 26 months (range, 15 to 42) after infusion of the gene-modified cells, all but 1 of the 13 patients who had a non-beta(0)/beta(0) genotype had stopped receiving red-cell transfusions; the levels of HbA(T87Q) ranged from 3.4 to 10.0 g per deciliter, and the levels of total hemoglobin ranged from 8.2 to 13.7 g per deciliter. Correction of biologic markers of dyserythropoiesis was achieved in evaluated patients with hemoglobin levels near normal ranges. In 9 patients with a beta(0)/beta(0) genotype or two copies of the IVS1-110 mutation, the median annualized transfusion volume was decreased by 73%, and red-cell transfusions were discontinued in 3 patients. Treatment-related adverse events were typical of those associated with autologous stem-cell transplantation. No clonal dominance related to vector integration was observed. CONCLUSIONS Gene therapy with autologous CD34+ cells transduced with the BB305 vector reduced or eliminated the need for long-term red-cell transfusions in 22 patients with severe beta-thalassemia without serious adverse events related to the drug product. (Funded by Bluebird Bio and others; HGB-204 and HGB-205 ClinicalTrials. gov numbers, NCT01745120 and NCT02151526.)
Published: 2018

11. Results from the Completed Hgb-205 Trial of Lentiglobin for β-Thalassemia and Lentiglobin for Sickle Cell Disease Gene Therapy

Author: Mariane de Montalembert, Elisa Magrin, Despina Moshous, Pablo Bartolucci, Marilyne Poirée, Fabrice Monpoux, Nicolas Hebert, David Grévent, Hervé Puy, Jean-François Meritet, Marina Cavazzana, Thibaud Lefebvre, Annarita Miccio, Isabelle Guichard, Catherine Poirot, Michaela Semeraro, Olivier Hermine, Erin Whitney, Felipe Suarez, Jean-Antoine Ribeil, Isabelle Funck-Brentano, Wassim El Nemer, Alessandra Magnani, Laure Joseph, François Lefrère, Valentine Brousse, Mohammed Asmal, Jean-Sebastien Diana, Bénédicte Neven, Philippe Bourget, Marisa Gayron, and Wenmei Huang
Subjects: medicine.medical_specialty, Blood transfusion, business.industry, Thalassemia, medicine.medical_treatment, Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, Sickle cell anemia, Hemoglobin A, Internal medicine, medicine, Bluebird Bio, Packed red blood cells, Adverse effect, business, Busulfan, medicine.drug
Abstract: Background LentiGlobin gene therapy contains autologous CD34+ hematopoietic stem cells (HSCs) transduced with the BB305 lentiviral vector (LVV), encoding human β-globin with a T87Q substitution. This substitution confers anti-sickling properties to the gene therapy-derived hemoglobin (HbAT87Q) and allows for its quantification in transduced HSCs. The proof of concept for LentiGlobin gene therapy in patients with transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) was established in the recently completed HGB-205 study (NCT02151526). Herein, we provide the safety and efficacy outcomes and long-term follow-up data for all 7 treated patients, 4 with TDT and 3 with SCD. Methods Patients 5−35 years old with TDT (≥ 100 mL/kg of packed red blood cells [pRBCs]/year) or severe SCD (e.g., ≥ 2 acute chest syndromes [ACS] or ≥ 2 vaso-occlusive crises in the preceding year or the year before regular transfusions) were enrolled. CD34+ HSCs were obtained by mobilization and apheresis in patients with TDT or by bone marrow harvest in patients with SCD. Following collection, cells were transduced with the BB305 LVV. Patients underwent busulfan myeloablative conditioning and were infused with transduced cells. Patients were monitored for engraftment, adverse events (AEs), HbAT87Q levels, and other hematologic and clinical parameters. After 2 years in HGB-205, patients transitioned into the long-term follow-up study, LTF-303 (NCT02633943). Summary statistics are shown as median (min-max). Results As of June 2019, patients with TDT (n=4) and SCD (n=3) had a median follow-up of 49.6 (40.5-60.6) and 28.5 (25.5-52.5) months, respectively. Table 1 shows patient and drug product characteristics and several key efficacy outcomes. All patients achieved HSC engraftment. LentiGlobin safety profile was consistent with busulfan myeloablative conditioning and, in case of SCD, with the underlying disease state. The most common non-hematologic Grade ≥ 3 AEs post-LentiGlobin gene therapy (≥ 2 patients) for patients with TDT were stomatitis (n=4) and increased aspartate aminotransferase (n=2), and for patients with SCD were ACS (n=2) and vaso-occlusive pain (n=2). In all 4 patients with TDT, total Hb and HbAT87Q levels remained generally stable up to 5 years post-LentiGlobin infusion. Three of 4 patients achieved transfusion independence (TI; defined as weighted average Hb ≥ 9g/dL without pRBC transfusions for ≥ 12 months), for an ongoing duration of 56.3 (38.2-57.6) months. Weighted average total Hb during TI was 11.4 (10.5-13.0) g/dL. One patient has been off transfusions for 37.5 months and had total Hb of 7.7 g/dL, which was below the ≥ 9 g/dL requirement to meet the protocol definition of TI. At last visit, HbAT87Q levels in these 4 patients ranged from 6.2-11.2 g/dL, which contributed 73.8-86.8% of the total Hb. The first patient treated with LentiGlobin for SCD experienced one vaso-occlusive pain episode, which developed at 30 months after LentiGlobin gene therapy following a case of acute gastroenteritis with fever and dehydration. The second SCD patient had 2 serious AEs (SAEs) of ACS approximately 6 and 8 months after LentiGlobin gene therapy. The patient resumed chronic pRBC transfusions and hydroxyurea treatment and subsequently experienced 2 SAEs of vaso-occlusive pain; no additional SAEs of vaso-occlusive pain or ACS were reported during the last 16 months of follow-up after LentiGlobin infusion. The third SCD patient had no episodes of vaso-occlusive pain or ACS during 25.5 months of follow-up post-LentiGlobin gene therapy as of the data cut-off. Two patients with SCD who have been off chronic pRBC transfusions, showed improvement in hemolysis markers post-LentiGlobin treatment and stabilization of HbAT87Q expression at approximately 6 months post-LentiGlobin infusion. Total Hb levels for patients with SCD at last visit were 13.0 g/dL (patient 1), 9.4 g/dL (patient 2), and 9.8 g/dL (patient 3), with corresponding HbAT87Q contributions of 47.9%, 7.9%, and 25.8%, respectively. Summary With up to 5 years of follow-up, treatment with LentiGlobin gene therapy was well tolerated and resulted in improvement in hematologic parameters and disease-related symptoms. Further results from the completed study will be presented. Disclosures Hermine: Celgene: Research Funding; Novartis: Research Funding; AB science: Consultancy, Equity Ownership, Honoraria, Research Funding. Brousse:bluebird bio, Inc: Consultancy; AddMedica: Consultancy. El Nemer:Hemanext: Other: Other. Bartolucci:Novartis: Membership on an entity's Board of Directors or advisory committees; AddMedica: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; HEMANEXT: Membership on an entity's Board of Directors or advisory committees. Asmal:bluebird bio, Inc: Employment, Equity Ownership. Whitney:bluebird bio, Inc: Employment, Equity Ownership. Gayron:bluebird bio, Inc: Employment, Equity Ownership. Huang:bluebird bio, Inc.: Employment, Equity Ownership. de Montalembert:AddMedica: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Ribeil:bluebird bio, Inc: Employment, Equity Ownership. Cavazzana:SmartImmune: Other: Founder.
Published: 2019

12. Is Intrapartum Intravenous Zidovudine for Prevention of Mother-to-Child HIV-1 Transmission Still Useful in the Combination Antiretroviral Therapy Era?

Author: Nelly Briand, Josiane Warszawski, Laurent Mandelbrot, Catherine Dollfus, Emmanuelle Pannier, Ludovic Cravello, Rose Nguyen, Isabelle Matheron, Norbert Winer, Roland Tubiana, Christine Rouzioux, Albert Faye, Stéphane Blanche, Françoise Meier, Dominique Duro, Marine Joras, Emmanuel Mortier, Catherine Crenn-Hebert, Corinne Floch-Tudal, Fabienne Mazy, Mariam Bensalah, Agnès Villemant-Uludag, Agnès Lefort, Virginie Zarrouk, Pierre-François Ceccaldi, Gisèle Philip, Gilles Hittinger, Martine Malet, Bruno Bachelard, Marie Medus, Joëlle Dendale-Nguyen, Jean-Pierre Brossier, Olivier Aubry, Jean-Luc Esnault, Sophie Leautez, Philippe Perré, Isabelle Suaud, Sandrine-Anne Martha, Mahfoud Rouha, Pascale Perfezou, Gilles Blondin, Charles Bellot, Séverine Ansart, Philippe Le Moine, Karine Bages-Jaffuel, Jean-Charles Duthé, Michel Garré, Sylvain Jaffuel, Corinne Daniel, Christian Calvez, Claude Beuscart, Emmanuelle Boutaric, Jennifer Rohan, Sylvie Lemoal, Linda Lassel, Ghislaine Cotten, Christelle Dupré, Esther Beauville, Cédric Arvieux, Anabèle Dos Santos, Corinne Cudeville, Yves Poinsignon, Virginie Mouton-Rioux, Gaétane Mousset, Anne Grellier, Philippe Moreau, Philippe Tillaut, Odile Luycx-Vaillant, Philippe de Morel, Marie-Françoise Le Coz, Isabelle Belzic, Mathilde Niault, Anne Vandenbergh, Cécile Janssen, Susanne Braig, Virginie Vitrat, Jacques Gaillat, Gaëlle Clavere, Jean-Pierre Bru, Blandine Peyret, Catherine Mullard, Marie Echard, Philippe Talon, Marion Dehlinger, Cécile Winter, Brigitte Heller-Roussin, Odile Launay, Maria Fouchet, Ghislaine Firtion, Isabelle Goupil, Nora Boudjoudi, Agnès Bourgeois-Moine, Marylène Bodard, Valérie Vivier, Mandovi Rajguru, Virginie Huri, Elie Azria, Sophie Matheron, Neila Elaoun, Philippe Faucher, Valérie Garrait, Christiane Komme, Isabelle Hau, Laurent Richier, Claudine Touboul, Valérie Thoirain, Laurent Cotte, Olivier Tariel, Joseph Koffi, Jean-Marc Labaune, Corinne Brochier, Denis Roux, Christophe Elleau, Camille Runel, Henri Bataille, Marie-Thérèse Sow, Ketty Samar, Blandine Muanza, Marc Duval, Clarisse Kingue-Ekollo, Bénédicte Carpentier, Isabelle Ronda, Jean-Marc Chamouilli, Natacha Entz-Werle, Hervé Seaume, Sarah Ducrocq, Philippe Bailly-Salin, Yvon Lemercier, Joëlle Tricoire, Alain Berrebi, Michèle Antras, Evelyne Armand, Claudine Cayla, François Bonnal, Catherine Chabanier, Anne Chacé, Sophie Couderc, Anne Boutemy, Marie-Christelle Dallot, Alain Al-Issa, Corinne Routier, Ahmed Zakaria, Véronique Favret, Juliette Gerbe, Elisabeth Questiaux, MariaLuisa Partisani, David Rey, Christine Cheneau, Christine Allisy, Dominique Brault, François Hervé, Marie-Gisèle Lebrette, Lise Selleret, Dieudonné Ekoukou, Pascal Bolot, Marie-Aude Khuong-Josses, Marie-Christine Allemon, Nelly Ghibaudo, Pierre Frange, Florence Veber, Delphine Lemercier, Marie-Christine Mourey, Gilles Blasquez, Michèle Granier, Houda Touahri, Alain Devidas, Israël Nisand, Michèle Weil, Christophe Vayssière, Jean-Luc Berger, Martine Munzer, Olivier Graesslin, Anne-Florence Naime-Alix, Frédérique Quetin, Anne Laubies, Manuela Bonmarchand, Jennifer Sommer, Patricia Bourse, Anne Coursol, Michel Youssef, Juliette Laurent, Mariem Raho, Véronique Chambrin, Philippe Labrune, Laure Clech, Alexandra Benachi, Bertrand Le Lorier, Isolde Pauly-Ravelly, Claude Allouche, Ama Johnson, Laurence Benoist, Catherine Delannoy, Eric Lachassine, Stéphanie Bolie, Joël Gaudelus, Vincent Jeantils, Amelie Benabara, Leïla Karaoui, Véronique Lefèvre, André Bongain, Eliane Galiba, Anne Deville, Fabrice Monpoux, Jacques Durant, Christian Aufrant, Jean Furioli, Jean-Louis Salomon, Françoise Granier, Antoine Doumet, Youssef Douadi, Jean Gondry, Jean-Luc Schmit, Brigitte Pautard, Marc Gamerre, Isabelle Thuret, Laurence Neimann, Claire Hubert, Bruno Carbonne, Geneviève Vaudre, Marie-Dominique Tabone, Didier Pinquier, Gaëlle Pinto Cardoso, Brigitte Clavier, Françoise Borsa-Lebas, Agathe De Lauzanne, Constance Borie, Sandrine Leveillé, Erianna Bellaton, Dominique Garion, Martine Levine, Claire Colmant, Cécile Goujard, Marc Tardieu, Florent Fuchs, Ikram Jrad, Delphine Peretti, Katia Bourdic, Corinne Fourcade, Catherine Chirouze, Jean-Marie Estavoyer, Robert Maillet, Véronique Reliquet, Cécile Brunet, Isabelle Reynaud, Claire Briandet, Jacques Brouard, Gaël Beucher, Pascale Goubin, Cécile Lanty, Eric Froguel, Béatrice Gourdel, Arnaud Chalvon Demersay, Gilbert Algava, Véronique Hentgen, Fabienne Messaoudi, Pascale Nau, Jean-Marc Besnier, Jérôme Potin, Nadine Taché, Yves Bertrand, Kamila Kebaïli, Véronique Ronat, Anne Fresard, Kareen Billiemaz, Ramona Abrudan, Alain Fournié, Jean-Marie Chennebault, Philippe Arsac, Nicole Ciraru-Vigneron, Geneviève Mouchnino, Dominique Ayral, Nelly Guigue, Muriel Lalande, Paul Benos, Christiane De Gennes, Sonia Chanzy, Valérie Isart, François Cazassus, Véronique Walter, François Bissuel, Yamina Hammou, Sophie d'Angelo, Faïza Ajana, Françoise Mazingue, Raymond Mezin, Yves Hatchuel, André Cabié, and Narcisse Elenga
Subjects: Adult, Male, Microbiology (medical), medicine.medical_specialty, Anti-HIV Agents, HIV Infections, Zidovudine, Pregnancy, Risk Factors, immune system diseases, medicine, Humans, Prospective Studies, Pregnancy Complications, Infectious, Antibiotic prophylaxis, Prospective cohort study, Chi-Square Distribution, Obstetrics, Transmission (medicine), Vaginal delivery, business.industry, Infant, Newborn, virus diseases, Antibiotic Prophylaxis, Viral Load, medicine.disease, Infectious Disease Transmission, Vertical, Surgery, Infectious Diseases, Cohort, Female, business, Viral load, medicine.drug
Abstract: BACKGROUND: Intrapartum intravenous zidovudine (ZDV) prophylaxis is a long-standing component of prevention of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in high-resource countries. In some recent guidelines, intravenous ZDV is no longer systematically recommended for mothers receiving combination antiretroviral therapy (cART) with low viral load. We evaluated the impact of intravenous ZDV according to viral load and obstetrical conditions. METHODS: All HIV-1-infected women delivering between 1 January 1997 and 31 December 2010 in the French Perinatal Cohort (ANRS-EPF) were analyzed if they received ART during pregnancy and did not breastfeed. We identified maternal and obstetrical characteristics related to lack of intravenous ZDV and compared its association with MTCT rate and other infant parameters, according to various risk factors. RESULTS: Intravenous ZDV was used in 95.2% of the 11 538 deliveries. Older age, multiparity, and preterm and vaginal delivery were associated with lack of intravenous ZDV (n = 554). In women who delivered with viral load ≥1000 copies/mL, the overall MTCT rate was higher without than with intravenous ZDV (7.5% vs 2.9%; P = .01); however, there was no such difference when the neonate received postnatal intensification therapy. Among them, 77% of women who had viral load
Published: 2013

13. Benefits of rituximab as a second-line treatment for autoimmune haemolytic anaemia in children: a prospective French cohort study

Author: Patrick Lutz, Guy Leverger, Isabelle Pellier, Eric Jeziorski, Aude Marie-Cardine, Marlène Pasquet, Corinne Armari-Alla, Nathalie Aladjidi, Brigitte Nelken, Christophe Piguet, Stéphane Ducassou, Hervé Chambost, Fanny Fouissac, Y Perel, Sophie Bayart, Alain Fisher, Helder Fernandes, Yves Bertrand, Marc Michel, Odile Lejars, Thierry Leblanc, Corinne Guitton, Philippe Vic, Fabrice Monpoux, CHU de Bordeaux Pellegrin [Bordeaux], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital de la Tronche, Service pédiatrique d'hématologie-oncologie, Hôpital Jeanne de Flandre [Lille], Unité d'Hémato-Immunologie pédiatrique [Hôpital Robert Debré, Paris], Service d'Immuno-hématologie pédiatrique [Hôpital Robert Debré, Paris], Hôpital Robert Debré-Hôpital Robert Debré, Service d'hématologie, immunologie biologiques et cytogénétique, Hôpital Bicêtre-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de pédiatrie, CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Hématogoie pédiatrique, hôpital Sud, Hôpital Charles Nicolle [Rouen], Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service d'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and CHU Rouen
Subjects: Male, medicine.medical_specialty, Evans syndrome, Adolescent, [SDV]Life Sciences [q-bio], Steroid withdrawal, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Blood Transfusion, Prospective Studies, Child, Complete response, ComputingMilieux_MISCELLANEOUS, Second line treatment, business.industry, Drug Substitution, Hematology, medicine.disease, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Child, Preschool, Immunology, National study, Hematinics, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, Female, Steroids, Anemia, Hemolytic, Autoimmune, France, business, 030215 immunology, Cohort study, medicine.drug
Abstract: Summary Childhood autoimmune haemolytic anaemia (AIHA) requires second-line immunosuppressive therapy in 30–50% of cases. It appears that rituximab is indicated in such circumstances. This prospective national study reports the practice, efficacy and tolerance of rituximab in children with isolated AIHA and AIHA in the setting of Evans syndrome (ES). Sixty-one children were given rituximab between 2000 and 2014. The median interval from diagnosis to rituximab was 9·9 [interquartile range (IQR) 1·6–28·5] months. Forty-six patients responded (75%) and the 6-year relapse-free survival (RFS) was 48%. Twenty patients relapsed at a median interval of 10·8 (IQR 3·9–18·7) months, rituximab allowed steroid withdrawal in 44/61 (72%) of children. In isolated AIHA, complete response and 6-year RFS were significantly higher than in ES (P
Published: 2016

14. Noninvasive Procedures to Evaluate Liver Involvement in HIV-1 Vertically Infected Children

Author: Albert Tran, Maria-Alessandra Rosenthal-Allieri, Anne Deville, Amandine Rubio, Emilie Huguon, Fabrice Monpoux, Eric Rosenthal, Régine Truchi, Valérie Triolo, and P. Boutte
Subjects: Blood Platelets, Male, medicine.medical_specialty, Pathology, Adolescent, Population, HIV Infections, Gastroenterology, Pharmacotherapy, Antiretroviral Therapy, Highly Active, Internal medicine, medicine, Humans, Aspartate Aminotransferases, Child, education, Liver injury, education.field_of_study, medicine.diagnostic_test, Reverse-transcriptase inhibitor, FibroTest, business.industry, Age Factors, medicine.disease, Infectious Disease Transmission, Vertical, Fatty Liver, Cross-Sectional Studies, Liver, Liver biopsy, Pediatrics, Perinatology and Child Health, Disease Progression, HIV-1, Feasibility Studies, Reverse Transcriptase Inhibitors, Female, Liver function, Chemical and Drug Induced Liver Injury, Transient elastography, business, Biomarkers, medicine.drug
Abstract: Objectives: Progressive liver injury is a concern in HIV-infected children exposed to long-term antiretroviral drugs and to the cytopathic effect of HIV. Yet liver biopsy is usually considered too invasive to be repeated in these patients. The aims of this study are to evaluate the feasibility of noninvasive hepatic investigations in HIV-1-infected children, assess the prevalence of signs of liver affection, and analyse the influence of the HIV disease severity and the exposure to antiretroviral therapy. Materials and Methods: A cross-sectional study conducted in 26 HIV-1 vertically infected children ages 8 to 18 years old. Liver function was assessed with standard serum biochemical markers, FibroTest, ActiTest, SteatoTest, Forns index, aspartate aminotransferase to platelet ratio index, ultrasound, and Fibroscan. Results: Nineteen (>60%) children had signs of liver affection on at least 1 of the test results: 13 (50%) had elevated liver enzymes, 15 (63%), 8 (33%), 5 (21%), and 5 (21%) had abnormal FibroTest, ActiTest, Forns index, and aspartate aminotransferase to platelet ratio index results, respectively. Four children (17%) had mild liver steatosis on ultrasound. Fibroscan measures were significantly higher in patients than in age-matched healthy children. Patients with elevated Fibroscan measures also had significantly higher FibroTest results. Age, HIV stage N in the Centers for Disease Control and Prevention classification and exposure duration to nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor drugs were the main risk factors for hepatotoxicity. Conclusions: More than half of our population of HIV-infected children had biological and/or radiological signs of liver affection. Regular follow-up of liver function is necessary in these patients, which is now possible with noninvasive procedures.
Published: 2009

15. 279. Clinical Outcomes of Gene Therapy with BB305 Lentiviral Vector for Sickle Cell Disease and β-Thalassemia

Author: Pablo Bartolucci, Michaela Semeraro, Stany Chrétien, Stéphane Blanche, Fabien Touzot, Laura Sandler, Mariane de Montalembert, Manfred G. Schmidt, Salima Hacein-Bey-Abina, Sandeep Soni, Olivier Hermine, Bénédicte Neven, Philippe Bourget, Christof von Kalle, Marina Cavazzana, François Lefrère, Yves Beuzard, Felipe Suarez, Wassim El Nemer, Corinne Pondarré, Elisa Magrin, Emmanuel Payen, Philippe Leboulch, Jean-Antoine Ribeil, and Fabrice Monpoux
Subjects: 0301 basic medicine, Pharmacology, business.industry, Genetic enhancement, Thalassemia, Cell, Disease, medicine.disease, Viral vector, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, Drug Discovery, Immunology, Genetics, Molecular Medicine, Medicine, business, Molecular Biology
Published: 2016

16. Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants

Author: Marie Laure Chaix, Danièle Douard, Corinne Floch, Catherine Bertone, Joelle Nicolas, Etienne Vilmer, Albert Faye, Fabrice Monpoux, Isabelle Thuret, Marie Jeanne Mayaux, Catherine Dollfus, Stéphane Blanche, Jean Paul Teglas, Christine Rouzioux, and Ghislaine Firtion
Subjects: Microbiology (medical), medicine.medical_specialty, HIV Infections, Risk Assessment, Virus, Acquired immunodeficiency syndrome (AIDS), Immunopathology, Endopeptidases, Epidemiology, Humans, Medicine, Family history, Sida, Asthma, biology, business.industry, Infant, Newborn, Infant, HIV Protease Inhibitors, medicine.disease, biology.organism_classification, Virology, HIV Reverse Transcriptase, Infectious Diseases, Mutation, Pediatrics, Perinatology and Child Health, HIV-1, RNA, Viral, Drug Therapy, Combination, Viral disease, business
Abstract: 19. Groothuis JR, Gutierrez KM, Lauer BA. Respiratory syncy-tial virus infection in children with bronchopulmonary dys-plasia. Pediatrics 1988;82:199–203.20. Hall CB, Hall WJ, Gala CL, MaGill FB, Leddy JP. Long-termprospective study in children after respiratory syncytial virusinfection. J Pediatr 1984;105:358–64.21. McConnochie K, Roghmann K. Parental smoking, presence ofolder siblings, and family history of asthma increase risk ofbronchiolitis. Am J Dis Child 1986;140:806–12.22. Wang EE, Law BJ, Boucher FD, et al. Pediatric InvestigatorsCollaborative Network on Infections in Canada (PICNIC)study of admission and management variation in patientshospitalized with respiratory syncytial viral lower respira-tory tract infection. J Pediatr 1996;129:390–5.23. Nachman SA, Navaie-Waliser M, Qureshi MZ. Rehospitaliza-tion with respiratory syncytial virus after neonatal intensivecare unit discharge: a 3-year follow-up. Pediatrics 1997;100:E8.24. Redding GJ, Braun S, Mayock D. Impact of respiratorysyncytial virus immune globulin in 1:996–1997: a local con-trolled comparison. Arch Pediatr Adolesc Med 1999;153:503–7.25. Health Canada. National Population Health Survey High-lights. Ottawa: Health Protection Branch, 1996/1997.26. Behrendt CE, Decker MD, Burch DJ, Watson PH. Interna-tional variation in the management of infants hospitalizedwith respiratory syncytial virus. International RSV StudyGroup. Eur J Pediatr 1998;157:215–20.27. Parrott RH, Kim HW, Arrobio JO, et al. Epidemiology ofrespiratory syncytial virus infection in Washington, DC: II.Infection and disease with respect to age, immunologic sta-tus, race and sex. Am J Epidemiol 1973;98:289–300.28. Simoes E, King S, Lehr M, Groothuis J. Preterm twins andtriplets: a high-risk group for severe repiratory syncytialvirus infections. Am J Dis Child 1993;147:303–6.
Published: 2002

17. Autoimmune and inflammatory manifestations occur frequently in patients with primary immunodeficiencies

Author: Alain Fischer, Johan Provot, Jean-Philippe Jais, Alexandre Alcais, Nizar Mahlaoui, Daniel Adoue, Nathalie Aladjidi, Zahir Amoura, Philippe Arlet, Corinne Armari-Alla, Brigitte Bader-Meunier, Vincent Barlogis, Sophie Bayart, Beatrice Beaurain, Yves Bertrand, Boris Bienvenu, Stéphane Blanche, Damien Bodet, Bernard Bonnotte, Raphaël Borie, Patrick Boutard, Claire Briandet, Jean-Paul Brion, Carolina Brito, Jacques Brouard, Emilie Catherinot, Olivia Chandesris, Sarah Cohen-Beaussant, Hélène Coignard-Biehler, Laurence Costes, Louis-Jean Couderc, Gérard Couillault, Virginie Courteille, Elodie Curlier, Geneviève de Saint Basile, François Demeocq, Nathalie de Vergnes, Catherine Devoldere, Anne Deville, Jean Donadieu, Eric Dore, Fabienne Dulieu, Isabelle Durieu, Christine Edan, Natacha Entz Werle, Claire Fieschi, Fanny Fouyssac, Pierre Frange, Vincent Gajdos, Lionel Galicier, Virginie Gandemer, Martine Gardembas, Catherine Gaud, Bernard Grosbois, Gaelle Guillerm, Eric Hachulla, Mohamed Hamidou, Sébastien Héritier, Olivier Hermine, Cyrille Hoarau, Bruno Hoen, Arnaud Hot, Sébastien Humbert, Arnaud Jaccard, Serge Jacquot, Rolland Jaussaud, Pierre-Yves Jeandel, Eric Jeziorski, Kamila Kebaili, Anne-Sophie Korganow, Philippe Labrune, Olivier Lambotte, Fanny Lanternier, Claire Larroche, Alain Le Quellec, Emmanuelle Le Moigne, Vincent Le Moing, Yvon Lebranchu, Marc Lecuit, Guillaume Lefevre, Richard Lemal, Philippe Le Moine, Valérie Li Thiao Te, Olivier Lortholary, Patrick Lutz, Aude Magerus-Chatinet, Marion Malphettes, Aude Marie-Cardine, Nicolas Martin Silva, Agathe Masseau, Christian Massot, Françoise Mazingue, Etienne Merlin, Gérard Michel, Frédéric Millot, Odile Minckes, Béatrice Monlibert, Fabrice Monpoux, Despina Moshous, Luc Mouthon, Martine Munzer, Bénédicte Neven, Raphaëlle Nove-Josserand, Eric Oksenhendler, Marie Ouachée-Chardin, Anne Pagnier, Jean-Louis Pasquali, Marlène Pasquet, Isabelle Pellier, Yves Perel, Antoinette Perlat, Capucine Picard, Christophe Piguet, Dominique Plantaz, Pierre Quartier, Frédéric Rieux-Laucat, Pascal Roblot, Pierre-Marie Roger, Pierre-Simon Rohrlich, Bruno Royer, Valéry Salle, Françoise Sarrot-Reynauld, Amélie Servettaz, Jean-Louis Stephan, Nicolas Schleinitz, Felipe Suarez, Laure Swiader, Sophie Taque, Caroline Thomas, Olivier Tournilhac, Caroline Thumerelle, Jean-Pierre Vannier, Jean-François Viallard, Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France - Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Collège de France (CdF), 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), Chaire Médecine expérimentale (A. Fischer), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), and 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)
Subjects: Adult, Male, Risk, 0301 basic medicine, Primary immunodeficiencies, Adolescent, T-Lymphocytes, Immunology, Population, Context (language use), medicine.disease_cause, Inflammatory bowel disease, Autoimmunity, Young Adult, 03 medical and health sciences, Prevalence, medicine, Humans, Immunology and Allergy, Age of Onset, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Child, education, Aged, Retrospective Studies, Aged, 80 and over, Autoimmune disease, Purpura, Thrombocytopenic, Idiopathic, education.field_of_study, business.industry, Common variable immunodeficiency, Autoimmune Cytopenia, autoimmunity, Immunologic Deficiency Syndromes, Infant, Middle Aged, Inflammatory Bowel Diseases, Prognosis, medicine.disease, Survival Analysis, 3. Good health, 030104 developmental biology, inflammation, Child, Preschool, Primary immunodeficiency, Female, France, business
Abstract: International audience; BACKGROUND:Primary immunodeficiencies (PIDs) are inherited diseases associated with a considerable increase in susceptibility to infections. It is known that PIDs can also predispose to cancer and immune diseases, including allergy, autoimmunity, and inflammation.OBJECTIVE:We aimed at determining the incidence of autoimmunity and inflammation in patients with PIDs.METHODS:We have retrospectively screened 2183 consecutive cases of PID in the Centre de Référence Déficits Immunitaires Héréditaires registry (CEREDIH; the French national PID registry) for the occurrence of autoimmunity and inflammation.RESULTS:One or more autoimmune and inflammatory complications were noted in 26.2% of patients, with a risk of onset throughout the patient's lifetime. The risk of autoimmune cytopenia was at least 120 times higher than in the general population, the risk of inflammatory bowel disease in children was 80 times higher, and the risk of other autoimmune manifestations was approximately 10 times higher. Remarkably, all types of PIDs were associated with a risk of autoimmune and inflammatory complications, although the greatest risk was associated with T-cell PIDs and common variable immunodeficiency. The occurrence of autoimmune disease is a negative prognostic factor for survival.CONCLUSIONS:Our results provide the basis for a detailed prospective evaluation of autoimmunity and inflammation in the context of PIDs, with a view to accurately assessing these risks and describing the possible effect of medical intervention.
Published: 2017

18. Increased risk of serious bacterial infections due to maternal immunosuppression in HIV-exposed uninfected infants in a European country

Author: Marie Medus, Vincent Gajdos, Laure Clech, Céline Goissen, Arnaud Chalvon Demersay, Virginie Zarouk, Louis Bernard, Pierre-François Ceccaldi, René-Charles Rudigoz, Patricia Murger, Philippe Le Moine, Catherine Chirouze, Mandovi Rajguru, Ludovic Cravello, Véronique Lefevre Elbert, Luminata Shneider, Guy Leverger, Tessa Goetghebuer, Kamila Kebaili, Eliane Galiba, Claudine Touboul, Françoise Meier, Didier Tardif, Dieudoné Ekoukou, Michèle Granier, Ahmed Zakaria, Corinne Cudeville, Laurence Benoist, Emilie Piet, Emmanuelle Vintejoux, Yves Hatchuel, Christophe Michau, Jean-Luc Schmidt, Michel Françoise, Claire Briandet, Stéphane Blanche, Philippe Bailly-Salin, Anne Vanderbergh, Jeanne Sibiude, Christiane Kommé, Benoît Martha, Camille Runel-Belliard, Claire Pluchart, Imad Nahri, Vincent Jeantils, François Hervé, Isabelle Hau, Agnès Lefort, Dominique Ayral, Delphine Peretti, Stéphanie Proust, Marie Belloy, Christine Rouzioux, Arnaud Boutet, Philippe Van de Perre, Elisabeth Broustal, Cécile Hafner Mauvais, Thierry Pistone, Marie-Dominique Tabone, Hélène Dauphin, Laurent Cotte, Clement Taron-Brocard, Jean-Marie Lang, Christine Boissinot, Antoine Doumet, André Bongain, Narcisse Elenga, Geneviève Mouchnino, Anne Boutemy, Christine Cheneau, Pascale Perfezou, Pierre Frange, Mathilde Niault, Christelle Dupre, Anne Chacé, Jean-Paul Teglas, Corinne Daniel, Sophie Matheron, Severine Ansart, Martine Levine, Fabienne Caby, Marc Duval-Arnould, Isabelle Metheron, Kareen Billiemaz, Albert Faye, Didier Armangaud, Yamina Hammou, Neila Elaoun, Anne Deville, Philippe Arsac, Lydie Sanchez, Odile Luycx Vaillant, Philippe Lumbroso, Marie-Gisèle Lebrette, Norbert Winer, Elise Maurel, Ramona Abrudan, Luc De Saint Martin, Françoise Jacquier, Christian Calvez, Fabrice Monpoux, Louis Mesnard, Marie-Aude Khuong-Josses, David Rey, Isabelle Belzic, Christine Allisy, Claire Genet, Hervé Seaume, Roland Tubiana, Jacques Reynes, Pascale Nau, Gilles Blondin, Eric Lachassine, Yves Poinsignon, Cédric Arvieux, Leila Karaoui, Anaïs Perilhou, Amélie Benbara, Marine Joras, Sophie Leautez-Nainville, Sophie Ducroix-Roubert, Raghad Moalim, Pascal Bolot, Jacques Gaillat, Olivier Bollengier Stragier, Alain Devidas, Muriel Lalande, Delphine Lemercier, Jean-Pierre Brossier, Emmanuelle Boutard, Isolde Pauly-Ravelly, Marie-Françoise Le Coz, Anne Grelier, Alain Alissa, Christiane De Gennes, Jean-Luc Delassus, Emmanuel Mortier, Faiza Ajana, Ghislaine Firtion, Alain Berrebi, Rose Nguyen, Sarah Ducrocq, Jean-Marc Chamouilli, Fabienne Mazy, Maïa Banigé, Khaled Mohamed, Natacha Entz-Werle, Jacques Brouard, Germaine Bachelard, Sandrine Delmas, Anne Constanty, Véronique Reliquet, Sophie Couderc, Florence Veber, Lahcene Allal, Catherine Crenn-Hebert, Blandine Muanza, Gaelle Pinto-Cardoso, Laurent Mandelbrot, Ama Johnson, Fabienne Messaoudi, Christian Burle, Josiane Warszawski, Bénédicte Carpentier, Dominique Brault, Suzanne Braig, Pascale Fialaire, Corinne Fourcade, Elisabeth Questiaux, Véronique Chambrin, Alain Lafeuillade, Véronique Hentgen, Yves Aubrard, Anne Borgne, Sandrine-Anne Martha, Evelyne Werner, Corinne Floch-Tudal, Agnès Bourgeois Moine, Corinne Routier, Jérôme Le Chenadec, Anne Coursol, Alain Fisher, Amélie Chabrol, Cécile Winter, Cécile Brunet-Cartier, Philippe Labrune, Claudine Cayla, Françoise Mazingue, Virginie Vitrat, Cyril Clavel, Michel Segondy, Ruxandra-Oana Calin, Lise Selleret, Pierre Weinbreck, Zaitoun Abdallah Moussa, Joël Gaudelus, Gaetane Mousset, Thomas Guimard, Agnès Villemant Uludag, Emmanuelle Pannier, Brigitte Clavier, Nicole Ciraru-Vigneron, Alain Checoury, Christophe Elleau, Manuela Bonmarchand, Catherine Dollfus, Joëlle Dendale-Nguyen, Adrien May, Pierre Chevojon, Claire Hubert, Constance Borie, Marialuisa Partisani, Elie Azria, Edouard Vaucel, Erianna Bellaton Marouts, Philippe Moreau, Jean-Luc Esnault, Mahfoud Rouha, Mary-France Courcoux, Brigitte Heller-Roussin, Gilles Hittinger, Christine Rouger, Lanto Ratsimbazafy, Jean-Marc Labaune, Mohamed Abdelhadi, Brigitte Elharrar, Joëlle Tricoire, Eric David, Hassan Safwan, Karine Guimard, Bruno Carbonne, Muriel Barat, Marion Dehlinger-Paul, Stéphane Bounan, Myriam Costa, Estelle Bauville, Didier Pinquier, Valérie Garrait, Etienne Dienga, Odile Launay, Zoha Maakroun, and Dominique Salmon Ceron
Subjects: Microbiology (medical), Pediatrics, medicine.medical_specialty, medicine.medical_treatment, Human immunodeficiency virus (HIV), HIV Infections, Kaplan-Meier Estimate, medicine.disease_cause, Infant, Newborn, Diseases, Pregnancy, medicine, Humans, Pregnancy Complications, Infectious, Retrospective Studies, business.industry, Proportional hazards model, Risk of infection, Hazard ratio, Infant, Newborn, Infant, Immunosuppression, Bacterial Infections, medicine.disease, Confidence interval, Infectious Disease Transmission, Vertical, CD4 Lymphocyte Count, Infectious Diseases, Immunology, Cohort, Female, France, business, Immunosuppressive Agents
Abstract: BACKGROUND Morbidity and mortality are higher among human immunodeficiency virus (HIV) exposed but uninfected (HEU) infants than unexposed infants, particularly if the mother had a low CD4 count. We investigated the possible association between maternal immune depression during pregnancy and the risk of infection in HEU infants in the national French Perinatal Cohort (EPF). METHODS All neonates, born alive, to HIV-1-infected women enrolled in the EPF between 2002 and 2010 were included. The primary outcome was the first serious (hospitalization or death) infection during the first year of life. The main exposure variable was maternal CD4 cell count near delivery. The Kaplan-Meier method and multivariate Cox models were applied, with the different types of infections managed as competing events. RESULTS Among 7638 HEU neonates, 699 had at least 1 serious infection (of which 159 were bacterial) with a Kaplan-Meier probability of 9.3% (95% confidence interval, 8.7-10.0) at 1 year. The risk of serious bacterial infection during the first year of life significantly increased with lower maternal CD4 cell count, before and after adjustment for maternal CD4 cell count
Published: 2014

19. Fusion of TEL, the ETS-Variant Gene 6 (ETV6), to the Receptor-Associated Kinase JAK2 as a Result of t(9; 12) in a Lymphoid and t(9; 15; 12) in a Myeloid Leukemia

Author: Mathijs Baens, Luc Van Rompaey, Pieter J. Peeters, Fabrice Monpoux, Herman Van den Berghe, Sophie Raynaud, Peter Marynen, Iwona Wlodarska, J. Grosgeorge, Jan Cools, and Patrick Philip
Subjects: Male, Oncogene Proteins, Fusion, Molecular Sequence Data, Immunology, Biology, Lymphocyte Activation, Polymerase Chain Reaction, Biochemistry, Translocation, Genetic, Receptor tyrosine kinase, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, medicine, Humans, Amino Acid Sequence, In Situ Hybridization, Fluorescence, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 12, ABL, Base Sequence, Infant, Myeloid leukemia, DNA, Neoplasm, Oncogenes, Cell Biology, Hematology, Precursor Cell Lymphoblastic Leukemia-Lymphoma, TEL-JAK2, medicine.disease, Fusion protein, ETV6, Cell Transformation, Neoplastic, biology.protein, Cancer research, Chromosomes, Human, Pair 9, Tyrosine kinase, Signal Transduction, Chronic myelogenous leukemia
Abstract: Translocations in hematologic disease of myeloid or lymphoid origin with breakpoints at chromosome band 12p13 frequently result in rearrangements of the Ets variant gene 6 (ETV6). As a consequence either the ETS DNA-binding domain or the Helix-Loop-Helix (HLH) oligomerization domain of ETV6 is fused to different partner genes. We show here that a t(9; 12)(p24; p13) in a case of early pre-B acute lymphoid leukemia and a t(9; 15; 12)(p24; q15; p13) in atypical chronic myelogenous leukemia in transformation involve the ETV6 gene at 12p13 and the JAK2 gene at 9p24. In each case different fusion mRNAs were found, with only one resulting in an open reading frame for a chimeric protein consisting of the HLH oligomerization domain of ETV6 and the protein tyrosine kinase (PTK) domain of JAK2. The cloning of the complete human JAK2 coding and genomic sequences and of the genomic junction fragments of the translocations allowed a characterization of the different splice events leading to the various mRNAs. JAK2 plays a central role in non–protein tyrosine kinase receptor signaling pathways, which could explain its involvement in malignancies of different hematologic lineages. Besides hop in Drosophila no member of the JAK family has yet been implicated in tumorigenesis.
Published: 1997

20. Congenital Leukemia Cutis Preceding Monoblastic Leukemia by 3 Months

Author: Yves Hatchuel, Roger Mariani, Paul Hofman, Sophie Raynaud, Fabrice Monpoux, Jean Paul Ortonne, Isabelle Sudaka, and Jean Philippe Lacour
Subjects: Male, Pathology, medicine.medical_specialty, Neutropenia, Biopsy, Cutis, Dermatology, Skin Diseases, Translocation, Genetic, Fatal Outcome, Bone Marrow, hemic and lymphatic diseases, medicine, Humans, Skin, Acute leukemia, integumentary system, medicine.diagnostic_test, business.industry, Infant, Newborn, Leukemia cutis, medicine.disease, Acute Monoblastic Leukemia, medicine.anatomical_structure, Leukemia, Monocytic, Acute, Pediatrics, Perinatology and Child Health, Skin biopsy, Bone marrow, medicine.symptom, business, Rare disease
Abstract: We report an infant born with a cutaneous nodular eruption and neutropenia. Skin biopsy specimens revealed an immature dermal infiltrate suggestive of leukemia cutis, but repeated peripheral blood and bone marrow examinations failed to demonstrate malignant cells. The eruption resolved spontaneously. At the age of 3 months, a second occurrence of maculopapular skin lesions led to discovery of an acute monoblastic leukemia with (9;11)(p21-22;q23) translocation. Congenital acute leukemia is a rare disease associated with skin infiltration in 25% to 30% of patients. Usually the diagnosis is easily made by peripheral blood examination and/or bone marrow aspirate. However, skin involvement may precede acute leukemia by several weeks. Although very rare, this event must be kept in mind.
Published: 1996

21. Protective effect of IgM against colonization of the respiratory tract by nontypeable Haemophilus influenzae in patients with hypogammaglobulinemia

Author: Julien Beauté, Pierre Galanaud, Pauline Brosselin, Capucine Picard, Romain Micol, Samer Kayal, Jean-Claude Lecron, Isabelle Pellier, Olivier Lambotte, Raphaele Nove-Josserand, Fabrice Monpoux, Nizar Mahlaoui, Fanny Lanternier, Stéphane Blanche, Anne Durandy, Caroline Thomas, Kamila Kebaili, Felipe Suarez, Marie-Alexandra Alyanakian, Pierre Teira, Olivier Lortholary, Yasmine Dudoit, Olivier Join-Lambert, Ioannis Theodorou, Alain Fischer, Alexandra Salmon, Marie-Dominique Tabone, Olivier Hermine, Marc Lecuit, Marianne Debré, Nathalie Aladjidi, Fabienne Dulieu, Gael Mouillot, Agathe Masseau, Eric Oksenhendler, Hélène Coignard-Biehler, Vincent Barlogis, Gaelle Obenga, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), 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'Hémato-oncologie Pédiatrique, CHU Bordeaux [Bordeaux]-Hôpital Pellegrin, Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hématologie et oncologie pédiatrique, 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), Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), service de médecine interne, Hôpital de Bicêtre, Service de Génétique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de médecine interne, Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Cytokines, chimiokines et immunopathologie, Université Paris-Sud - Paris 11 (UP11)-IFR13-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'immunologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie cellulaire et tissulaire, Modélisations pharmacocinétiques-pharmacodynamiques pour un meilleur usage des anti-infectieux, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), INSERM 980, Laboratory of Human Genetics of Infectious Disease, Laboratory of Human Genetics of Infectious Disease, Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm 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), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Developpement Normal et Pathologique du Système Immunitaire, Laboratoire du D eveloppement Normal et Pathologique du Syst eme Immunitaire, Unit e d'Immunologie et H ematologie P ediatrique, French Ministry of Health to the Rare Diseases National Reference Centre for Primary Immune Deficiencies (CEREDIH), INSERM, Assistance Publique-Hôpitaux de Paris [grant no. P060308], senior ERC grant 'PIDIMMUN' [grant no. 249816], ARC (Association pour la Recherche sur le Cancer), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Brébion, Alice, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Institut Pasteur du Cambodge-Réseau International des Instituts Pasteur ( RIIP ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre hospitalier universitaire de Nantes ( CHU Nantes ), Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ) -Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers, Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Université Paris-Sud - Paris 11 ( UP11 ) -IFR13-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Pathogénie des infections systémiques ( UMR_S 570 ), 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 Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Pharmacologie des anti-infectieux, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Laboratoire d'hématologie ( ERL 8254 ), 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 ) -Centre National de la Recherche Scientifique ( CNRS ), Equipe avenir Microorganismes et Barrières de l'Hôte, and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, MESH : Hyper-IgM Immunodeficiency Syndrome, MESH : Risk, Respiratory System, MESH : Prospective Studies, immunoglobulins, Antibodies, Viral, Hyper-IgM Immunodeficiency Syndrome, medicine.disease_cause, Haemophilus influenzae, Hypogammaglobulinemia, 0302 clinical medicine, MESH : Child, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Agammaglobulinemia, MESH: Child, Immunology and Allergy, MESH : Female, Prospective Studies, infections, MESH: Incidence, Child, Immunodeficiency, IgM deficiency, MESH: Respiratory System, 0303 health sciences, MESH: Risk, Respiratory tract infections, MESH : Haemophilus Infections, Incidence, MESH : Incidence, MESH: Immunoglobulin M, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Female, medicine.symptom, Antibody, MESH: Haemophilus Infections, MESH : Antibodies, Viral, Risk, Haemophilus Infections, IgM, Adolescent, MESH : Immunoglobulin M, MESH : Male, Immunology, Biology, 03 medical and health sciences, MESH : Agammaglobulinemia, MESH : Adolescent, medicine, MESH : Haemophilus influenzae, Humans, MESH: Agammaglobulinemia, MESH : Respiratory System, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, MESH: Adolescent, Bronchiectasis, MESH: Humans, MESH : Humans, MESH: Haemophilus influenzae, medicine.disease, MESH: Male, MESH: Prospective Studies, Immunoglobulin M, MESH: Hyper-IgM Immunodeficiency Syndrome, biology.protein, Sputum, immunodeficiency, MESH: Female, MESH: Antibodies, Viral, 030215 immunology
Abstract: International audience; BACKGROUND: Primary immunoglobulin deficiencies lead to recurrent bacterial infections of the respiratory tract and bronchiectasis, even with adequate immunoglobulin replacement therapy. It is not known whether patients able to secrete IgM (eg, those with hyper-IgM [HIgM] syndrome) are as susceptible to these infections as patients who lack IgM production (eg, those with panhypogammaglobulinemia [PHG]). OBJECTIVE: This study is aimed at identifying specific microbiological and clinical (infections) characteristics that distinguish immunoglobulin-substituted patients with PHG from patients with HIgM syndrome. METHODS: A cohort of patients with HIgM syndrome (n = 25) and a cohort of patients with PHG (n = 86) were monitored prospectively for 2 years while receiving similar polyvalent immunoglobulin replacement therapies. Regular bacterial analyses of nasal swabs and sputum were performed, and clinical events were recorded. In parallel, serum and saliva IgM antibody concentrations were measured. RESULTS: When compared with patients with PHG, patients with HIgM syndrome were found to have a significantly lower risk of nontypeable Haemophilus influenzae carriage in particular (relative risk, 0.39; 95% CI, 0.21-0.63). Moreover, patients with HIgM syndrome (including those unable to generate somatic hypermutations of immunoglobulin genes) displayed anti-nontypeable H influenzae IgM antibodies in their serum and saliva. Also, patients with HIgM syndrome had a lower incidence of acute respiratory tract infections. CONCLUSIONS: IgM antibodies appear to be microbiologically and clinically protective and might thus attenuate the infectious consequences of a lack of production of other immunoglobulin isotypes in patients with HIgM syndrome. Polyvalent IgG replacement therapy might not fully compensate for IgM deficiency. It might thus be worth adapting long-term antimicrobial prophylactic regimens according to the underlying B-cell immunodeficiency phenotype.
Published: 2012

22. Real Life HAART Efficacy in Chronically HIV-1 Infected Children 15-Year Follow-Up

Author: Charlotte Sakarovitch, Christian Pradier, Eric Fontas, Fabrice Monpoux, Jacqueline Cottalorda-Dufayard, and ine Rubio
Subjects: medicine.medical_specialty, business.industry, Immunology, Human immunodeficiency virus (HIV), Dermatology, medicine.disease_cause, Omics, medicine.disease, Regimen, Infectious Diseases, Acquired immunodeficiency syndrome (AIDS), Virology, Internal medicine, Cohort, medicine, Retrospective analysis, Protease inhibitor (pharmacology), Observational study, business
Abstract: Background: It is now widely accepted that the antiretroviral first line-treatment basis in HIV-1 infected children is a combination of 2 nucleoside reverse transcriptase inhibitors and 1 protease inhibitor or 1 non NRTI. However, after few months or years, some patients presented with virological failure. Objective: Using a “real life conditions” cohort, we aimed to study the median duration of Viral Controlled Replication (VCR) and the factors associated with failure in infected children. Methods: Thirty six HIV-1 infected patients were followed between September 1996 and September 2010. Children were included starting from the date of initiation of their first successful HAART. Duration of effective VCR was defined as a length, in months, from inclusion to virological failure defined as a HIV-1 PCR-RNA higher than 400 c/ml. Results: The overall median VCR duration was 46.2 months. Duration was significantly shorter in patients: previously exposed to mono therapies, with CD4 count lower than 350 and with PI-based HAART. After adjustment, the negative effect of PI-based HAART regimen compared to nNRTI-based HAART remained significant (HR=5.7 [95%CI=1.43-22.7]). Conclusion: Therefore, retrospective analysis of “real life” condition data in observational cohort may contribute to a better understanding of non optimal virological care.
Published: 2012

23. Management of Newborns from HIV-1 Seropositive Mothers: Results of a Single Center Implementation of the French National Guidelines

Author: Christian Dageville, Herve Haas, André Bongain, Amandine Rubio, Fabrice Monpoux, and Alice Moulin
Subjects: medicine.medical_specialty, Medical treatment, business.industry, Immunology, Human immunodeficiency virus (HIV), Dermatology, medicine.disease_cause, Single Center, Omics, Infectious Diseases, Pharmacotherapy, ANTIRETROVIRAL AGENTS, Virology, Medicine, business, Intensive care medicine
Published: 2012

24. Pulmonary Function in HIV-1 Vertically Infected Children

Author: Fabrice Monpoux, M. Albertini, Dominique Crenesse, Amandine Rubio, and Carole Bailly
Subjects: Spirometry, medicine.medical_specialty, education.field_of_study, Lung, medicine.diagnostic_test, business.industry, Incidence (epidemiology), Immunology, Population, Dermatology, medicine.disease, Gastroenterology, Pulmonary function testing, FEV1/FVC ratio, Infectious Diseases, medicine.anatomical_structure, Virology, Internal medicine, medicine, education, business, Viral load, Asthma
Abstract: Background: Despite reports of an increasing incidence of asthma in HIV-infected children, exploration of pulmonary function by spirometry has never been reported in this population in the HAART era. Objective: The aim of this study was to determine the prevalence of spirometric abnormalities in HIV-1 infected children. We conducted a cross-sectional study of pulmonary function tests (PFT) in HIV-1 vertically infected children. Methods: Spirometric values were measured in 17 HIV-1 chronically infected children and compared to matched healthy children. In HIV-1 infected children, the correlations between PFT and the determination of the single breath carbon monoxide diffusing capacity of the lung (TL CO ) and immunological and virological values were assessed. Results: Overall, 11 of the 17 PFT were normal. Four showed mild distal obstruction. Two were considered restrictive. When compared with matched healthy children, the only difference was the FEV1/FVC ratio that was significantly lower in the patients’ group (91.9% of predicted value versus 97.1%, p
Published: 2012

25. Outcomes of Gene Therapy for Severe Sickle Disease and Beta-Thalassemia Major Via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral Beta AT87Q-Globin Vector

Author: Stéphane Blanche, Fabien Touzot, Stany Chrétien, Philippe Leboulch, Olivier Hermine, Fabrice Monpoux, Manfred Schmidt, Mariane de Montalembert, Frans A. Kuypers, Laura Sandler, Salima Hacien-Bey-Abina, Felipe Suarez, Resy Cavallesco, François Lefrère, Philippe Bourget, Sandeep Soni, Jean-Antoine Ribeil, Yves Beuzard, Bénédicte Neven, Christof von Kalle, Emmanuel Payen, Marina Cavazzana, and Corinne Pondarré
Subjects: medicine.medical_specialty, Blood transfusion, Neutrophil Engraftment, business.industry, medicine.medical_treatment, Immunology, Cell Biology, Hematology, Biochemistry, Bone marrow purging, Transplantation, Hemoglobin A, Internal medicine, medicine, LentiGlobin BB305, Transfusion therapy, business, Busulfan, medicine.drug
Abstract: Background: In patients with hemoglobinopathies, hematopoietic stem cell (HSC) gene therapy has the potential to induce production of functional β-globin in the red blood cell lineage with the aim of reducing or eliminating the symptoms of disease. Previous results from 1 subject with severe sickle cell disease (SCD; 6 months follow-up) and 2 subjects with β0/βE-thalassemia major (up to 15 months follow-up) treated in clinical study HGB-205 suggested that transplantation with autologous CD34+ cells transduced with the LentiGlobin BB305 lentiviral vector containing an engineered βA-T87Q-globin gene (LentiGlobin BB305 Drug Product) resulted in near-normal levels of total hemoglobin (Hb) and rapid clinical improvement. Here we provide data on a new subject enrolled and additional follow-up data on the 3 subjects previously presented in Study HGB-205. Subjects and Methods: Subjects with severe SCD underwent HSC collection via bone marrow harvest, while subjects with β-thalassemia major underwent HSC collection via peripheral blood apheresis following mobilization. CD34+ cells were selected and transduced with LentiGlobin BB305 lentiviral vector to produce the drug product. Subjects underwent myeloablation with intravenous busulfan, followed by infusion of drug product. Subjects were monitored for hematological engraftment, vector copy number, βA-T87Q-globin expression, adverse events and transfusion requirements. Integration site analysis (ISA) and replication-competent lentivirus (RCL) assays were performed. Prophylactic RBC transfusions were continued in subjects with SCD who were on chronic transfusion pre-transplant to maintain HbS Results: As of 31 July 2015, 1 subject with severe SCD (Subject 1204, βS/βS with multiple vaso-occlusive crises, silent infarct, acute chest syndrome, and on prophylactic transfusions) and 3 subjects withβ-thalassemia major (Subjects 1201, 1202 and 1203) have been infused with the LentiGlobin BB305 Drug Product. The outcome of these subjects to date is shown in Table 1. No subject has experienced a drug product-related adverse event, and ISA analyses demonstrate highly polyclonal reconstitution without clonal dominance. The subject with severe SCD is producing approximately 51.5% of anti-sickling hemoglobin (48% HbAT87Q, 1.8% HbF, 1.7% HbA2) at 9 months post-infusion. This subject has not had a post-infusion hospitalization for a SCD-related event despite stopping chronic transfusions at Day +88. Both subjects with β0/βE-thalassemia major have remained transfusion-free for at least 15 months post-infusion, with a consistent expression of βA-T87Q-globin; the subject with β0/β0-thalassemia major has only had 1 month follow-up post-drug product infusion to date. Conclusion: The subject with severe SCD is producing approximately 51.5% anti-sickling globins with HbS of 48.5% and remains free of SCD-related events despite stopping chronic transfusion therapy. Two subjects with β0/βE-thalassemia major remain transfusion-free for at least 15 months post infusion of LentiGlobin BB305 Drug Product. Gene therapy using autologous HSC transduced with LentiGlobin BB305 lentiviral vector is a promising approach for the treatment of patients with hemoglobinopathies. Table 1. Demographics and Transplantation Outcomes Subject Age (years)/ Sex (M/F) Genotype BB305 Drug Product Day of Neutrophil Engraftment Drug Product- related Adverse Events Day of Last pRBC Transfusion Last Study Visit (Months) Hb at Last Visit (g/dL) VCNa CD34+ cell dose (x106 per kg) Subject with severe sickle cell disease HbAT87Q/HbF/ HbS/Total Hb 1204 13/ M βS/βS 1.2 / 1.0 5.6 Day +37 None Day +88 9M 5.5/0.2/5.5/11.4 Subjects with β-thalassemia major Hb AT87Q/ Total Hb 1201 18/ F β0/βE 1.5 8.9 Day +13 None Day +10 18M 7.8/10.7 1202 16/ M β0/βE 2.1 13.6 Day +15 None Day +12 15M 9.7/12.8 1203 19/ M β0/β0 0.8 8.8 Day +28 None Day +15 1M Pending/9.2 As of 31 July 2015 aVCN, vector copy number; F=female; M= Male for gender, and months for day of last follow-up Disclosures Payen: bluebrid bio: Consultancy. Beuzard:bluebird bio Inc: Consultancy, Equity Ownership. von Kalle:bluebird bio, Inc.: Consultancy. Sandler:bluebird bio, Inc.: Employment, Equity Ownership. Soni:bluebird bio, Inc.: Employment, Equity Ownership. De Montalembert:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Leboulch:bluebird bio: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.
Published: 2015

26. Multiphenotypic Acute Leukemias: Clinicopathologic Correlations and Response to Therapy

Author: Gilbert C. Faure, Jacques Bayle, Patrick Philip, Marie C. Béné, Francoise Baudouin, Fabrice Monpoux, and Isabelle Sudaka
Subjects: Adult, Cancer Research, Pathology, medicine.medical_specialty, Myeloid, Adolescent, Response to therapy, Immunophenotyping, Antigen, Antigens, CD, Precursor cell, parasitic diseases, medicine, Humans, Child, Aged, Aged, 80 and over, Leukemia, business.industry, Infant, Hematology, Middle Aged, Prognosis, medicine.disease, Survival Rate, Phenotype, medicine.anatomical_structure, Oncology, Child, Preschool, Acute Disease, Cohort, lipids (amino acids, peptides, and proteins), business
Abstract: Multiphenotypic acute leukemias (MAL), defined by the coexpression on most blast cells of antigens classically attributed to different lineages, remain a rare event. We isolated a series of 26 such cases from a cohort of 1565 leukemic patients whose cells were immunophenotyped at diagnosis. Markers of B and myeloid lineage (BM) were associated in 16 cases (62%), 3 coexpressed B and T markers (BT), and T-cell and myeloid antigens (TM) were found in 7 (27%). A tumoral syndrome was observed in 69% of the patients, without significant differences between the immunophenotypic subgroups. Median event free survivals in the three immunophenotypic subgroups as defined were respectively 24 months for BM-MAL, 4 months for TM-MAL and 7 months for BT-MAL respectively. The poorer prognosis of TM-MAL was significantly different from that of BM-MAL (p < 0.001). This concurred with the poorer prognosis associated with CD7 expression or absence of CD10, both characteristic features of TM-MAL.
Published: 1992

27. Transient elastography (Fibroscan) in HIV-1 vertically infected children. A cross-sectional study

Author: Anne Deville, Albert Tran, Valérie Riolo, Emilie Huguon, Amandine Rubio, P. Boutte, Régine Truchi, and Fabrice Monpoux
Subjects: lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Pathology, medicine.diagnostic_test, Liver toxicity, Cross-sectional study, business.industry, Human immunodeficiency virus (HIV), virus diseases, Sampling error, Gold standard (test), medicine.disease_cause, Infectious Diseases, Virology, Internal medicine, Liver biopsy, medicine, business, Transient elastography, Hepatic fibrosis, lcsh:RC581-607
Abstract: Progressive liver toxicity is a concern in HIV-infected patients. Although liver biopsy remains the gold standard for liver assessment, its invasiveness, sampling errors, variability in interpretation and expense do not make it an ideal routine follow-up exam. During the last decade, new non-invasive tools have been developed for the assessment of hepatic fibrosis in HCV and HIV/HCV co-infected patients.
Published: 2009

28. [Maternal-fetal transmission of HIV and after care of infants in pediatrics]

Author: Fabrice, Monpoux, Marie, Soumah, Christel, Falzon, and Pascale, Cozzi
Subjects: Adolescent, Anti-HIV Agents, Infant, Newborn, Aftercare, Infant, HIV Infections, Nurse's Role, Pediatrics, Infectious Disease Transmission, Vertical, Pediatric Nursing, Primary Prevention, Perinatal Care, Neonatal Screening, Patient Education as Topic, Pregnancy, Risk Factors, Child, Preschool, Humans, Female, France, Pregnancy Complications, Infectious, Child
Published: 2009

29. Partial Splenectomy in a Child With Human Immunodeficiency Virus-Related Immune Thrombocytopenia

Author: Jean-Yves Kurzenne, P. Boutte, Fabrice Monpoux, Nicolas Sirvent, and Jacqueline Cottalorda
Subjects: Male, medicine.medical_specialty, Anti-HIV Agents, medicine.medical_treatment, Splenectomy, HIV Infections, Spleen, Acquired immunodeficiency syndrome (AIDS), Immunopathology, medicine, Humans, Platelet, Sida, Purpura, Thrombocytopenic, Idiopathic, biology, Platelet Count, business.industry, Infant, Hematology, Viral Load, biology.organism_classification, medicine.disease, CD4 Lymphocyte Count, Surgery, medicine.anatomical_structure, Oncology, Lamivudine, Pediatrics, Perinatology and Child Health, Drug Therapy, Combination, Viral disease, Complication, business, Zidovudine
Abstract: Immune thrombocytopenia (IT) is a frequently occurring disease in childhood and a well known complication of HIV infection. Splenectomy is a part of the treatment strategy for severe chronic IT. However, overwhelming infections after splenectomy have limited its use, especially in young children. A 7-year-old child with maternal-fetal HIV-I infection and related thrombocytopenia underwent splenectomy after previous treatment failed to improve her platelet count. Approximately 75% of the spleen was removed. The postoperative period was uncomplicated, and the platelet count increased significantly to greater than 500,000/mm 3 . Ultrasonographic examination performed 3 months later showed a stable volume of the spleen stump (40 × 40 × 20 mm) with effective vascularization. The platelet count 12 months after surgery showed a sustained increase greater than 150,000 cell/mm 3 . Subtotal splenectomy may be a safe and effective alternative for patients with HIV and immune thrombocytopenia.
Published: 1999

30. Rituximab therapy for childhood Evans syndrome

Author: Antoine Pariente, Brigitte Bader-Meunier, Brigitte Nelken, Fabrice Monpoux, Corinne Armari-Alla, Francoise Bellmann, Martine Munzer, Capucine Picard, Nathalie Aladjidi, Yves Perel, Arnaud Chaussé, Karima Yacouben, Yves Bertrand, Alain Robert, Francoise LeDeist, and Guy Leverger
Subjects: Male, medicine.medical_specialty, Evans syndrome, Adolescent, Anemia, Prednisolone, Infections, Gastroenterology, Disease-Free Survival, Antibodies, Monoclonal, Murine-Derived, Prednisone, Immunopathology, Internal medicine, medicine, Humans, Immunologic Factors, Registries, Child, Survival rate, Cytopenia, Purpura, Thrombocytopenic, Idiopathic, business.industry, Remission Induction, Antibodies, Monoclonal, Infant, Hematology, Syndrome, medicine.disease, Survival Rate, Child, Preschool, Immunology, Rituximab, Female, Anemia, Hemolytic, Autoimmune, France, Autoimmune hemolytic anemia, business, medicine.drug, Follow-Up Studies
Abstract: The safety and efficacy of rituximab have been retrospectively assessed in 17 children with Evans syndrome. Patients received 4 or 3 weekly doses of rituximab (375 mg/m(2) per dose) associated with prednisone, alone (14 patients) or associated with other immunosuppressive drugs. Complete or partial remission of at least one cytopenia was achieved in 13 out of the 17 patients (76%), and lasted in 11 of them with a mean follow-up of 2.4 years (range 0.5-7 years). Steroid therapy was stopped or tapered at 50-100% of the baseline dosage in all long-term responders. Moderate side effects and infection occurred only in 4 and 1 children respectively.
Published: 2007

31. Long-term nonprogression of HIV infection in children: evaluation of the ANRS prospective French Pediatric Cohort

Author: Joëlle Tricoire, Fabrice Monpoux, Laurence Meyer, Josiane Warszawski, Christine Rouzioux, Ghislaine Firtion, Jérome Lechenadec, Danielle Douard, Catherine Dollfus, Albert Faye, Yassine Benmebarek, and Stéphane Blanche
Subjects: Microbiology (medical), Pediatrics, medicine.medical_specialty, Time Factors, Adolescent, Anti-HIV Agents, HIV Infections, Kaplan-Meier Estimate, Asymptomatic, Cohort Studies, Acquired immunodeficiency syndrome (AIDS), medicine, Humans, Sida, Prospective cohort study, Child, biology, business.industry, HIV Long-Term Survivors, Infant, biology.organism_classification, medicine.disease, Infectious Diseases, El Niño, Child, Preschool, Cohort, Disease Progression, HIV-1, France, medicine.symptom, business, Zidovudine, Cohort study, Follow-Up Studies
Abstract: BACKGROUND Some children who are infected with human immunodeficiency virus type 1 (HIV-1) during the perinatal period remain asymptomatic for very long periods in the absence of antiretroviral treatment, as is the case for some adults. Our objective was to estimate the proportion of children who developed neither symptoms nor major immunological perturbations to the age of > or = 10 years in a prospective cohort of infected children who had been observed since birth. METHODS The ongoing prospective French Pediatric Cohort includes 568 HIV-1-infected children. Here, we report the follow-up data for all 348 HIV-1-infected children who were born before 1 January 1994. Children with long-term nonprogression of infection (LTNPs) were defined as HIV-1-infected children who had been observed for at least 10 years, never received antiretroviral treatment other than zidovudine monotherapy, never developed symptoms of Centers for Disease Control and Prevention clinical category C or B, and had a CD4+ cell percentage of < 25% no more than once during follow-up. Other definitions were compared. RESULTS The Kaplan-Meier estimate of long-term nonprogression was 2.4% (95% confidence interval, 1.1%-4.6%) at 10 years of age, and 7 children were classified as LTNPs. The Kaplan-Meier estimates decreased slightly with age, to 1.8% at 12 years of age and 1.4% at 14 years of age. Plasma HIV-1 replication rates were low (< 1000 copies RNA/mL) for 2 of the 7 LTNPs at the age of 10 years (0.6% of the total denominator). None of the routinely measured maternal or perinatal markers were significantly linked to long-term nonprogression, with the exception of the mother's Centers for Disease Control and Prevention clinical category at the time of delivery. CONCLUSIONS Approximately 2% of children who were infected during the perinatal period displayed no immunological or clinical progression by the age of 10 years. This figure is close to that reported for adults in studies that have used similar definitions.
Published: 2007

32. Study Hgb-205: Outcomes of Gene Therapy for Hemoglobinopathies Via Transplantation of Autologous Hematopoietic Stem Cells Transduced Ex Vivo with a Lentiviral βΑ-T87Q-Globin Vector (LentiGlobin® BB305 Drug Product)

Author: Fabien Touzot, Corrine Pondarre, Mariane de Montalembert, Olivier Hermine, Jean-Antoine Ribeil, Laura Sandler, Sandeep Soni, Philippe Leboulch, Emmanuel Payen, Marina Cavazzana, Resy Cavallesco, Phillipe Bourget, Christof von Kalle, Stany Chrétien, François Lefrère, Bénédicte Neven, Manfred Schmidt, Fabrice Monpoux, Stephanie Blanche, Felipe Suarez, Salima Hacein-Bey-Abina, and Yves Beuzard
Subjects: Oncology, medicine.medical_specialty, Blood transfusion, Neutrophil Engraftment, business.industry, Genetic enhancement, medicine.medical_treatment, Immunology, Cell Biology, Hematology, Biochemistry, Bone marrow purging, Transplantation, Internal medicine, medicine, LentiGlobin BB305, business, Busulfan, Ex vivo, medicine.drug
Abstract: Background : In patients with β-thalassemia major, hematopoietic stem cell (HSC) gene therapy has the potential to induce production of β-globin, γ-globin or modified β-globin in the red blood cell lineage and reduce or stop the need for blood transfusions. We have previously presented early results for 2 subjects with β/βE -thalassemia major that suggested that transplantation with autologous CD34+ cells transduced with a replication-defective, self-inactivating LentiGlobin BB305 lentiviral vector containing an engineered β-globin gene (βA-T87Q) resulted in near-normal levels of total hemoglobin (Hb) early after HSC infusion. Herein, we provide additional follow-up data on these two subjects. Subjects and Methods : After obtaining informed consent, subjects with β-thalassemia major underwent HSC collection via peripheral blood apheresis and CD34+ cells were selected. Estimation of the mean ex- vivo vector copy number (VCN) was obtained by quantitative PCR performed on pooled colony-forming progenitors. Subjects underwent myeloablation with intravenous busulfan, followed by infusion of transduced CD34+ cells. Subjects were monitored for hematological engraftment, βA-T87Q-globin expression (by high performance liquid chromatography) and transfusion requirements. Integration site analysis (ISA, by linear amplification-mediated PCR and high-throughput sequencing on nucleated cells) and replication-competent lentivirus (RCL) assays were performed. Results: As of 31 July 2014, two subjects with β0/βE thalassemia major (Subjects 1201 and 1202) have undergone infusion with drug product. The outcome of these two subjects to date is shown in Table 1. The initial safety profile is consistent with myeloablation, without serious adverse events or drug product-related adverse events. Both subjects remain transfusion independent. ISA analyses in both the subjects at 3 months shows polyclonal reconstitution. An additional 2 subjects have been enrolled in this study but have not yet undergone drug product infusion. Conclusion: In the first two subjects, early transfusion independence was achieved and has been maintained as of 31 July 2014. Further follow up data on these two subjects and additional data on subjects who have undergone drug product infusion in this study will be presented. Gene therapy using autologous HSC transduced with LentiGlobin BB305 lentiviral vector is a promising approach for the treatment of patients with β-thalassemia major. | Subject | Age (years) and gender | Genotype | BB305 Drug Product | Day of Neutrophil Engraftment | Drug Product-related Adverse Events | Day of last pRBC transfusion | Day of last follow up | βA-T87Q-Hb at last follow-up visit /Total Hb (g/dL) | | ------- | ----------------------------- | -------- | ------------------ | ----------------------------- | ----------------------------------- | ---------------------------- | --------------------- | --------------------------------------------------- | -------- | | VCNa | CD34+ cell dose (x106 per kg) | | 1201 | 19 F | β/βE | 1.5 | 8.9 | Day +13 | None | Day +10 | Day +180 | 7.2/10.2 | | 1202 | 16 M | β/βE | 2.1 | 13.6 | Day +15 | None | Day +12 | Day +90 | 6.8/11.0 | Abstract 4797. Table 1. Preliminary Results of Dosing Parameters and Transplantation Outcomes As of 31 July 2014 a VCN, mean vector copy number Disclosures Payen: bluebird bio, Inc: Consultancy. Beuzard: bluebird bio, Inc: Consultancy, Equity Ownership. Sandler: bluebird bio, Inc: Employment, Equity Ownership. Soni: bluebird bio, Inc.: Employment, Equity Ownership. De Montalembert: Novartis : Speakers Bureau. Leboulch: bluebird bio: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding.
Published: 2014

33. Treatment interruption for virological failure or as sparing regimen in children with chronic HIV-1 infection

Author: Fabrice, Monpoux, Joelle, Tricoire, Muriel, Lalande, Veronique, Reliquet, Benedicte, Bebin, and Isabelle, Thuret
Subjects: Male, Adolescent, Genotype, HIV Infections, CD4 Lymphocyte Count, Withholding Treatment, Risk Factors, Antiretroviral Therapy, Highly Active, Child, Preschool, Chronic Disease, Mutation, HIV-1, Humans, RNA, Viral, Female, Treatment Failure, Child, Retrospective Studies
Abstract: To assess both benefits and risks related to treatment interruption (TI) in children with chronic HIV-1 materno-fetal infection.: A multicentre, retrospective analysis in five university hospital pediatric departments in France.Clinical events, plasma HIV-1 RNA, CD4 cell counts, CD4 percentages (CD4%) and genotypes were recorded in 24 patients before and during TI. Patients were classified as sparing regimen or virological failure groups according to the main reason for treatment interruption. Clinical events, immuno-virological evolution and genotype reversions were monitored.After a median of 40 weeks of TI, none of the patients presented with an AIDS-defining event. For the whole cohort, median viral load variation from baseline, measured during TI was +1.26 log10 copies/ml (range, -0.22, +4.3 log10) with large inter-individual variability, median absolute CD4 cell loss was 32.5% (range, -82, +17%). These variations were not different in the two patient groups. The mean number of mutations conferring resistance to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors at baseline and last evaluation did not differ significantly. Few mutation reversions to wild type were noted in our cohort.Treatment interruption in children with chronic HIV-1 infection is associated with higher viral load increases than observed in adult patients. The CD4 cell loss is comparable. Although no clinical AIDS-defining event was noted close monitoring is required when TI is proposed to HIV-infected children. Very few reversion mutations were observed during treatment interruption.
Published: 2004

34. Early versus deferred antiretroviral multidrug therapy in infants infected with HIV type 1

Author: Jérôme Le Chenadec, Stéphane Blanche, Albert Faye, Martine Levine, Danièle Douard, Joelle Nicolas, Isabelle Thuret, Marc Tardieu, Christine Rouzioux, Joëlle Tricoire, Fabrice Monpoux, Ghislaine Firtion, Eric Lachassinne, Marie Jeanne Mayaux, and Catherine Dollfus
Subjects: Microbiology (medical), Pediatrics, medicine.medical_specialty, Time Factors, Opportunistic infection, Encephalopathy, HIV Infections, Disease, Acquired immunodeficiency syndrome (AIDS), Medicine, Humans, Prospective Studies, Risk factor, Sida, biology, business.industry, Infant, biology.organism_classification, medicine.disease, Prognosis, Survival Rate, Infectious Diseases, Anti-Retroviral Agents, Cohort, Immunology, Disease Progression, HIV-1, Drug Therapy, Combination, Viral disease, business
Abstract: Background. The clinical impact of early antiretroviral multidrug therapy on the risk of early-onset severe human immunodeficiency virus (HIV) disease has not been evaluated on a large scale. Methods. We evaluated the risk of early-onset events associated with acquired immunodeficiency syndrome (AIDS), particularly the risk of encephalopathy, among infants in the French Perinatal Cohort, according to whether antiretroviral multidrug therapy was initiated before or after the age of 6 months. Results. Of 83 HIV-infected infants born in 1996 (when HAART became available) or later, 40 received early treatment on or before the age of 6 months, and 43 received deferred multidrug therapy after the age of 6 months. In the group that received early multidrug therapy, no child developed an opportunistic infection or an encephalopathy during the first 24 months of life. In the deferred multidrug therapy group, 6 infants presented with a total of 7 AIDS-associated events ( ), 3 of which were encephalopathies ( ). The small number of P p .01 P p .08 events prevented the identification of clinical and biological markers that accurately predict progression of earlyonset severe HIV disease. Conclusion. In this observational study, infants who received multidrug therapy before 6 months of age did not have the early-onset severe form of childhood HIV disease. Further studies are needed to find accurate early markers of disease progression in this age group.
Published: 2004

35. Relation of the Course of HIV Infection in Children to the Severity of the Disease in Their Mothers at Delivery

Author: C Courpotin, Etienne Vilmer, Ghislaine Firtion, J Tricoire, Françoise Meier, Claude Griscelli, Christine Rouzioux, Jean-François Delfraissy, Jean-Paul Teglas, Marie-Jeanne Mayaux, Stéphane Blanche, Fabrice Monpoux, and Nicole Ciraru-Vigneron
Subjects: CD4-Positive T-Lymphocytes, Risk, Pediatrics, medicine.medical_specialty, AIDS Dementia Complex, AIDS-Related Opportunistic Infections, HIV Core Protein p24, Human immunodeficiency virus (HIV), HIV Infections, Disease, medicine.disease_cause, Leukocyte Count, Acquired immunodeficiency syndrome (AIDS), Pregnancy, Confidence Intervals, medicine, Humans, Prospective Studies, Pregnancy Complications, Infectious, Risk factor, Prospective cohort study, Relation (history of concept), Immunodeficiency, business.industry, Infant, Newborn, Infant, Obstetrics and Gynecology, General Medicine, Delivery, Obstetric, medicine.disease, Cohort, Immunology, HIV-1, Female, Viral disease, business
Abstract: Among infants with maternally transmitted human immunodeficiency virus (HIV) infection, there are two patterns of disease progression. In about a fifth of these infants there is a rapid progression to profound immunodeficiency, whereas in the majority the disease progresses much more slowly.We studied the clinical and biologic characteristics of the mothers of infants infected with HIV type 1 (HIV-1) in the French Prospective Multicenter Cohort. Infection in the children was confirmed by serologic tests at the age of 18 months or by death from the acquired immunodeficiency syndrome at an earlier age. Only the 162 infected infants who could be followed for at least 18 months or until death were included in the analysis.The risk of opportunistic infections or encephalopathy in the first 18 months was 50 percent in the infants of mothers with class IV disease, according to the Centers for Disease Control and Prevention classification, and 14 percent in the infants of mothers with class II or III disease (relative risk, 3.6; 95 percent confidence interval, 1.8 to 7.3; P0.002). Forty-four percent of the former infants and 9 percent of the latter died before 18 months (relative risk, 4.7; 95 percent confidence interval, 2.1 to 10.4; P0.002). The risk of death correlated inversely with the mother's CD4+ cell count and directly with her HIV-1 p24 antigen level at delivery. There was also a direct correlation between the mother's CD4+ cell count and that of the infant at one, three, and nine months of age (correlation coefficient at nine months [n = 44], 0.48; P0.002). HIV-1 p24 antigen was detected more often in the infants whose mothers also had the antigen.In infants whose HIV infection is maternally acquired, the rate of disease progression varies directly with the severity of the disease in the mother at the time of delivery.
Published: 1994

36. Subcutaneous Interleukin-2 Therapy in a Child With Vertically Transmitted HIV-1 Infection

Author: Fabrice Monpoux, Patrick Philip, Nicolas Sirvent, Jacqueline Cottalorda, and P. Boutte
Subjects: Interleukin 2, Oncology, business.industry, Pediatrics, Perinatology and Child Health, Immunology, Human immunodeficiency virus (HIV), medicine, Hematology, medicine.disease_cause, business, medicine.drug
Published: 2003

37. Rituximab in 42 Cases of French Childhood Auto-Immune Haemolytic Anaemia: High Efficiency but Caution Required

Author: Ducassou, Stéphane, primary, Aladjidi, Nathalie, additional, Pondarre, Corinne, additional, Leblanc, Thierry, additional, Chambost, Hervé, additional, Corinne, Armari-Alla, additional, Marlene, Pasquet, additional, Fernandes, Helder, additional, Sophie, Bayart, additional, Christophe, Piguet, additional, Fanny, Fouyssac, additional, Fabrice, Monpoux, additional, Lejars, Odile, additional, Eric, Jeziorski, additional, Guitton, Corinne, additional, Leverger, Guy, additional, and Perel, Yves, additional
Published: 2011
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38. Inversion (14)(q11q32) in a case of acute myeloid leukemia expressing lymphoid-associated antigens

Author: Fabrice Monpoux, Noel Ayraud, Benedicte Brunet, Jacques Bayle, Sophie Raynaud, and Patrick Philip
Subjects: Cancer Research, Leukemia, Antigen, Genetics, medicine, Cancer research, Myeloid leukemia, Biology, medicine.disease, Molecular Biology, Inversion (discrete mathematics), Chromosomal inversion
Published: 1993

39. Acute basal ganglia necrosis associated with cytarabine therapy

Author: Bernard Diaine, Laurent Benet, Christian Richelme, Roger Mariani, Fabrice Monpoux, and Nicolas Sirvent
Subjects: Cancer Research, Pathology, medicine.medical_specialty, Text mining, Oncology, business.industry, Pediatrics, Perinatology and Child Health, medicine, Cytarabine, Basal ganglia necrosis, business, medicine.drug
Published: 1998

40. Exploration du métabolisme phospho-calcique chez l'enfant et l'adolescent présentant une infection VIH-1 chronique de transmission materno-foetale

Author: Bara, Éva, Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), and Fabrice Monpoux
Subjects: ostéopénie, enfants, VIH, Vitamine D, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, PTH
Abstract: INTRODUCTION : Des études réalisées en population adulte rapportent une morbidité plus importante chez les personnes infectées par le VIH présentant une carence en vitamine D. L'infection par le VIH serait un facteur de risque d'ostéopénie. Le métabolisme phospho-calcique est central chez l'enfant en période de croissance. Il nous semble indispensable de connaître le statut vitaminique D et de rechercher des modifications du métabolisme phospho-calcique dans notre population d'enfants infectés par le VIH afin d'avoir l'attitude préventive la plus adaptée. MÉTHODE : Étude monocentrique prospective au GCS-CHU Lenval Nice du 01/06/2010 au 01/05/2012. Les paramètres auxologiques et les dosages de la calcémie, 25-OH-D et 1,25(OH)2D, PAL, PTH, calciurie et TRP ont été réalisés de façon trimestrielle lors du suivi de chaque enfant. L'évaluation des apports calciques était réalisée à partir de questionnaires standardisés. RÉSULTATS : 69 dosages de 25-OH-D ont été réalisés chez 23 patients âgés de 4,5 à 18,5 ans. 25% des dosages montraient des calcémies basses et 22% un hyperparathyroïdisme. Les enfants au stade SIDA étaient carencés en 25-OH-D dans 55% contre 22% des cas lorsqu'ils n'étaient pas au stade SIDA (p=0,045). L'été, le sexe féminin et l'origine caucasienne étaient associés à un meilleur statut vitaminique D. 88,2% des enfants présentaient des apports en calcium inférieurs aux apports recommandés pour l'âge. Les patients traités par Efavirenz présentaient des PAL significativement plus élevées que ceux qui ne prenaient pas ce traitement (p=0,035). La 1,25(OH)2D était significativement plus basse chez les enfants traités par IP (p
Published: 2013

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