Author: "Immunovirologie et polymorphisme génétique" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Immunovirologie et polymorphisme génétique"' showing total 59 results

Start Over Author "Immunovirologie et polymorphisme génétique"

59 results on '"Immunovirologie et polymorphisme génétique"'

1. Paediatric sarcoidosis

Author: Nadia Nathan, Chiara Sileo, Alain Calender, Yves Pacheco, Paul-André Rosental, Catherine Cavalin, Odile Macchi, Dominique Valeyre, Annick Clement, Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie de l'immunodépression associée aux réponses inflammatoires systémiques - EA 7426 (PI3), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre d'études européennes et de politique comparée (Sciences Po, CNRS) (CEE), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Hôpital Avicenne [AP-HP], Hypoxie et Poumon : pneumopathologies fibrosantes, modulations ventilatoires et circulatoires (H&P), UFR SMBH-Université Sorbonne Paris Nord, Centre d'histoire de Sciences Po (CHSP), Sciences Po (Sciences Po), Centre d'études européennes et de politique comparée (CEE), Centre National de la Recherche Scientifique (CNRS)-Sciences Po (Sciences Po), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'histoire de Sciences Po (Sciences Po) (CHSP), Service de Génétique Moléculaire et Clinique, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de Recherche Interdisciplinaire en Sciences Sociales (IRISSO), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris Dauphine-PSL, Pneumologie Pédiatrique, AP-HP-CHU Trousseau [APHP], Physiopathologie des maladies génétiques d'expression pédiatrique, Immunovirologie et polymorphisme génétique, Université de Nantes (UN), Service des maladies respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, CCSD, Accord Elsevier, Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire interdisciplinaire d'évaluation des politiques publiques (Sciences Po) (LIEPP), Institut National de la Recherche Agronomique (INRA)-Université Paris Dauphine-PSL, and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)
Subjects: Pulmonary and Respiratory Medicine, disease, Granuloma, Adolescent, Sarcoidosis, Infant, Interstitial lung disease, [SHS.SCIPO]Humanities and Social Sciences/Political science, [SHS]Humanities and Social Sciences, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Sarcoidosis, Pulmonary, 030228 respiratory system, Child, Preschool, Pediatrics, Perinatology and Child Health, Disease Progression, Humans, Genetic Predisposition to Disease, [SHS] Humanities and Social Sciences, 030212 general & internal medicine, Child, Lung, Children
Abstract: International audience; Paediatric sarcoidosis is an extremely rare disease characterized by a granulomatous inflammation. The estimated incidence is 0.6–1.02/100,000 children, but in the absence of international registers, the disease is probably under-reported. Its pathophysiologic basis is not clearly understood but the current hypothesis is a combination of a genetic predisposition and an environmental exposure that could be either organic or mineral. Contrary to adult forms of the disease, general symptoms are often at the forefront at diagnosis. In its most frequent form, paediatric sarcoidosis is a multi-organ disorder affecting preferentially the lungs, the lymphatic system and the liver, but all organs can be affected. This review aims to provide an overview of current knowledge on sarcoidosis in children, providing a summary of the data available from cohort studies on the presentation, the management and the evolution of the disease in this specific population.
Published: 2019
Full Text: View/download PDF

2. Decrease of blood anti-alpha 1,3 Galactose Abs levels in multiple sclerosis (MS) and clinically isolated syndrome (CIS) patients

Author: Le Berre, L., Roussé, J., Gourraud, P-A, Imbert-Marcille, B-M, Salama, A., Evanno, G., Semana, G., Nicot, A., Dugast, E., Guerif, P., Adjaoud, C., Freour, T., Brouard, S., Agbalika, F., Marignier, R., Brassat, D., Laplaud, D-A, Drouet, Emmanuel, van Pesch, V., Soulillou, J-P, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-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 ), Etablissement français du sang [Rennes] (EFS Bretagne), Médecine et Biologie du Développement et de la Reproduction, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), European Union Seventh Framework Programme (FP7) [603,049], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and 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)
Subjects: Adult, Male, Epstein-Barr Virus Infections, Adolescent, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, multiple sclerosis, Young Adult, Pregnancy, EBV, Humans, Child, Aged, 3gal, Microbiota, Galactose, infectious mononucleosis, anti-neu5gc, Middle Aged, Anti-α1, 3 gal, Child, Preschool, Immunoglobulin G, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, anti-alpha 1, Demyelinating Diseases
Abstract: International audience; The etiology of multiple sclerosis (MS) remains elusive. Among the possible causes, the increase of anti-Neu5Gc antibodies during EBV primo-infection of Infectious mononucleosis (IMN) may damage the integrity of the blood-brain barrier facilitating the transfer of EBV-infected B cells and anti-EBV T cell clones in the brain. We investigated the change in titers of anti-Neu5Gc and anti-α1,3 Galactose antibodies in 49 IMN, in 76 MS, and 73 clinically isolated syndrome (CIS) patients, as well as age/gender-matched healthy individuals. Anti-Gal and anti-Neu5Gc are significantly increased during IMN (p=0.02 and p
Published: 2017
Full Text: View/download PDF

3. Impact of Graft-Versus-Graft Natural Killer Cell Alloreactivity on Single Unit Dominance After Double Umbilical Cord Blood Transplantation

Author: Laurence Lodé, David Senitzer, Marc Bonneville, Philippe Moreau, Christelle Volteau, Julie Esbelin, Catherine Willem, Anne Cesbron, Nolwenn Legrand, Patrice Chevallier, Pauline Rettman, Christelle Retière, Katia Gagne, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Etablissement Français du Sang [Nantes], Plateforme de Biométrie [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire d'Hématologie Biologique [Hôpital Hôtel-Dieu, Nantes], Hôpital Hôtel-Dieu [Nantes] (Centre Hospitalier Universitaire de Nantes), Hôpital Mère-Enfant [Hôpital Hôtel Dieu, Nantes], Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), 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), Division of Hematology and Bone Marrow Transplantation [Duarte, California, USA], City of Hope National Medical Center-City of Hope Comprehensive Cancer Center [Duarte], This work was supported by EFS Pays de la Loire and by grants from International Research Group on unrelated HEmatopoietic stem cell Transplantation (IRGHET 2009, IRGHET 2014), Association Recherche et Transfusion 2009 (ART 2009), Agence de la BioMédecine (ABM 2011, ABM 2014), Etablissement Français du Sang (EFS 2011-06, EFS 2014-06), Ligue contre le Cancer Grand Ouest 2013, LabEx Transplantex 2014, Association Leucémie Espoir Atlantique Famille (LEAF) and Nantes Atlantique Greffe de Moëlle Osseuse (NAGMO). PR is a PhD student supported by a EFS PL/Region Pays de la Loire grant., and Bernardo, Elizabeth
Subjects: 0301 basic medicine, Cytotoxicity, Immunologic, Genotype, Cell, Graft vs Host Disease, [SDV.CAN]Life Sciences [q-bio]/Cancer, Apoptosis, Cord Blood Stem Cell Transplantation, Human leukocyte antigen, Biology, Lymphocyte Activation, Natural killer cell, 03 medical and health sciences, fluids and secretions, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, HLA Antigens, medicine, Humans, Receptor, Cells, Cultured, Retrospective Studies, Transplantation, Umbilical Cord Blood Transplantation, Receptors, KIR3DL1, Histocompatibility, Killer Cells, Natural, 030104 developmental biology, medicine.anatomical_structure, Phenotype, Treatment Outcome, Cord blood, Immunology, embryonic structures, France, 030215 immunology
Abstract: International audience; BACKGROUND:Natural killer (NK) cell alloreactivity is favored after double umbilical cord blood transplantation (dUCBT) in which cord blood (UCB) units and patients are often HLA class I mismatched. Generally, only 1 UCB unit persists after dUCBT. We hypothesize, that NK cell alloreactivity mediated by killer cell immunoglobulin-like receptor (KIR)-HLA interactions may explain the dominance of 1UCB unit over the other after dUCBT.METHODS:We investigated the impact of KIR NK cell alloreactivities on the dominance of 1 full UCB unit in 50 dUCBT. We analyzed the effects of the KIR/HLA genetic incompatibilities and studied cord blood cells at both the phenotypic and functional levels.RESULTS:The genetic combination of KIR3DL1 loser UCB unit/Bw4 winner UCB unit determined both the dominance of 1 UCB unit (hazards ratio, 2.88 [1.32-6.27], P = 0.0077) and correlated with an increased incidence of relapse (hazards ratio, 4.91 [1.39-17.3], P = 0.0134). It is interesting to note that cord blood cells exhibited extremely low HLA class I expression. Moreover, resting cord blood KIR3DL1 NK cells exhibited a basal alloreactivity against Bw4 target cells that increased upon activation, thus triggering death by apoptosis.CONCLUSIONS:Our unicentric study suggests, for the first time, the significant impact of KIR NK cell alloreactivity in the determination of which UCB unit will dominate in dUCBT.
Published: 2016
Full Text: View/download PDF

4. HLA Reduces Killer Cell Ig-like Receptor Expression Level and Frequency in a Humanized Mouse Model

Author: Allan Thompson, John Trowsdale, David H. Raulet, Christelle Retière, Daniela C.F. Salvatori, Frits Koning, Melissa van Pel, Jeroen van Bergen, Leiden University Medical Center (LUMC), Etablissement Français du Sang [Nantes], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), University of California [Berkeley], University of California, University of Cambridge [UK] (CAM), University of California [Berkeley] (UC Berkeley), University of California (UC), and RETIERE, Christelle
Subjects: Genetically modified mouse, Receptor expression, Transgene, Immunology, Cell, Mice, Transgenic, chemical and pharmacologic phenomena, HLA-C Antigens, Human leukocyte antigen, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Lymphocyte Depletion, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Receptors, KIR, medicine, otorhinolaryngologic diseases, Animals, Humans, Immunology and Allergy, Receptor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Mice, Knockout, 0303 health sciences, H-2 Antigens, Models, Immunological, hemic and immune systems, Molecular biology, Killer Cells, Natural, Mice, Inbred C57BL, medicine.anatomical_structure, Receptors, KIR2DL2, Humanized mouse, Mice, Inbred CBA, NK Cell Lectin-Like Receptor Subfamily C, 030215 immunology
Abstract: NK cells use NK cell receptors to be able to recognize and eliminate infected, transformed, and allogeneic cells. Human NK cells are prevented from killing autologous healthy cells by virtue of inhibitory NKRs, primarily killer cell Ig-like receptors (KIR) that bind “self” HLA class I molecules. Individual NK cells stably express a selected set of KIR, but it is currently disputed whether the fraction of NK cells expressing a particular inhibitory KIR is influenced by the presence of the corresponding HLA ligand. The extreme polymorphism of the KIR and HLA loci, with wide-ranging affinities for individual KIR and HLA allele combinations, has made this issue particularly hard to tackle. In this study, we used a transgenic mouse model to investigate the effect of HLA on KIR repertoire and function in the absence of genetic variation inside and outside the KIR locus. These H-2Kb−/− and H-2Db−/− mice lacked ligands for inhibitory Ly49 receptors and were transgenic for HLA-Cw3 and a KIR B haplotype. In this reductionist system, the presence of HLA-Cw3 reduced the frequency of KIR2DL2+ cells, as well as the surface expression levels of KIR2DL2. In addition, in the presence of HLA-Cw3, the frequency of NKG2A+ cells and the surface expression levels of NKG2A were reduced. In line with these findings, both transgene-encoded KIR and endogenous NKG2A contributed to the rejection of cells lacking HLA-Cw3. These findings support the idea that HLA influences the human KIR repertoire.
Published: 2016
Full Text: View/download PDF

5. Impact of KIR/HLA genetic combinations on double umbilical cord blood transplantation outcomes. Results of a French multicentric retrospective study on behalf of the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) and the Société Francophone d'Histocompatibilité et d'Immunogénétique (SFHI)

Author: F Quainon, Evelyne Marry, C Retière, J.-F. Eliaou, A. Parissiadis, O Avinens, A Boudifa, Dominique Masson, N Legrand, Nicole Raus, Ibrahim Yakoub-Agha, A Batho, P Rettman, Florent Delbos, David Senitzer, Anne Kennel, A. Dormoy, Xavier Lafarge, Anne Devys, L. Absi, I Theodorou, M de Matteis, Anne Cesbron, M Drouet, Pascale Loiseau, Florent Malard, M Fort, Katia Gagne, Christophe Picard, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), ArcelorMittal Maizières Research SA, ArcelorMittal, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Alpes-Méditerranée (EFS - Alpes-Méditerranée), Etablissement Français du Sang, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Etablissement Français du Sang Nouvelle Aquitaine [Bordeaux] (EFS Bordeaux Nouvelle Aquitaine), Etablissement français du sang [Nice] (EFS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Paul Painlevé (LPP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Groupe Immunité des Muqueuses et Agents Pathogènes (GIMAP), Université Jean Monnet - Saint-Étienne (UJM), Etablissement français du sang [Clermont-Ferrand] (EFS), 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), Etablissement français du sang [Caen], Ambiances, Architectures, Urbanités (AAU ), École Centrale de Nantes (ECN)-École nationale supérieure d'architecture de Nantes (ENSA Nantes)-École nationale supérieure d'architecture de Grenoble (ENSAG)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Etablissement Français du Sang - Grand Est (EFS - alsace strasbourg), Développement du Systeme 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), CHU Limoges, City of Hope National Medical Center, Registre France Greffe de Moelle [Saint-Denis La Plaine] (RFGM), Agence de la biomédecine [Saint-Denis la Plaine], Service d'hématologie [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Etablissement Français du Sang [Nantes], Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Arcelor Research S.A, Arcelor, Laboratoire d'Immunologie, CHU Saint-Eloi, Anthropologie bio-culturelle, Droit, Ethique et Santé ( ADES ), Aix Marseille Université ( AMU ) -EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique ( CNRS ), Etablissement Français du Sang - Alpes-Méditerranée ( EFS - Alpes-Méditerranée ), Etablissement français du sang [Besançon] ( EFS ), Centre de Transfusion Sanguine Aquitaine-Limousin ( CTS AQUITAINE-LIMOUSIN ), Centre de Transfusion Sanguine, Etablissement français du sang [Nice] ( EFS ), Laboratoire Paul Painlevé - UMR 8524 ( LPP ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Groupe Immunité des Muqueuses et Agents Pathogènes ( GIMAP ), Université Jean Monnet [Saint-Étienne] ( UJM ), 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 ), Ambiances architecturales et urbaines ( AAU ), Ministère de la Culture et de la Communication ( MCC ) -École nationale supérieure d'architecture de Grenoble ( ENSAG ) -École nationale supérieure d'architecture de Nantes ( ENSA Nantes ) -École Centrale de Nantes ( ECN ) -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 ), Laboratoire d'allergologie, Centre Hospitalier Universitaire d'Angers, Registre France Greffe de Moelle [Saint-Denis La Plaine] ( RFGM ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Biologie des Organismes et Ecosystèmes Aquatiques ( BOREA ), Université des Antilles ( UA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut de Recherche pour le Développement ( IRD ) -Muséum National d'Histoire Naturelle ( MNHN ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Laboratoire Paul Painlevé - UMR 8524 (LPP), Université Jean Monnet [Saint-Étienne] (UJM), Centre National de la Recherche Scientifique (CNRS)-Université de Lille, École nationale supérieure d'architecture de Nantes (ENSA Nantes)-Ministère de la Culture et de la Communication (MCC)-École nationale supérieure d'architecture de Grenoble (ENSAG)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Nantes (ECN), Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Université de Caen Normandie (UNICAEN), and Normandie Université (NU)-Normandie Université (NU)
Subjects: 0301 basic medicine, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Human leukocyte antigen, 03 medical and health sciences, 0302 clinical medicine, Receptors, KIR, HLA Antigens, Transplantation Immunology, Humans, Medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Progenitor cell, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, Gynecology, Transplantation, [ SDV ] Life Sciences [q-bio], business.industry, Umbilical Cord Blood Transplantation, French, Retrospective cohort study, Hematology, medicine.disease, humanities, language.human_language, 3. Good health, Treatment Outcome, 030104 developmental biology, Graft-versus-host disease, Immunology, language, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cord Blood Stem Cell Transplantation, France, Stem cell, business, 030215 immunology
Abstract: Impact of KIR/HLA genetic combinations on double umbilical cord blood transplantation outcomes. Results of a French multicentric retrospective study on behalf of the Societe Francophone de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC) and the Societe Francophone d’Histocompatibilite et d’Immunogenetique (SFHI)
Published: 2016
Full Text: View/download PDF

6. Apoptosis characterizes immunological failure of HIV infected patients

Author: Cécile Brunet-François, Damien Ernst, Guy-Bart Stan, Raphaël Fonteneau, Virginie Ferré, Claude H. Moog, Marie-José Mhawej, François Raffi, Institut de Recherche en Communications et en Cybernétique de Nantes (IRCCyN), Mines Nantes (Mines Nantes)-École Centrale de Nantes (ECN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Liège, Department of Electrical Engineering and Computer Science (Institut Montefiore), Centre hospitalier universitaire de Nantes (CHU Nantes), Control Group of the Department of Engineering, University of Cambridge [UK] (CAM), Maladies Infectieuses, and Université de Nantes (UN)
Subjects: 0209 industrial biotechnology, Human immunodeficiency virus (HIV), immunological failure, 02 engineering and technology, medicine.disease_cause, Virus, [SPI.AUTO]Engineering Sciences [physics]/Automatic, 03 medical and health sciences, 020901 industrial engineering & automation, Acquired immunodeficiency syndrome (AIDS), Medicine, Electrical and Electronic Engineering, clinical trial, Sida, 030304 developmental biology, 0303 health sciences, biology, biomedical systems, business.industry, Applied Mathematics, apoptosis, HIV, identifiability, biology.organism_classification, medicine.disease, 3. Good health, Computer Science Applications, Clinical trial, Control and Systems Engineering, Apoptosis, Lentivirus, Immunology, Non linear systems, identification, Viral disease, parameter estimation, business
Abstract: International audience; This paper studies the influence of apoptosis in the dynamics of the HIV infection. A new modeling of the healthy CD4+ T-cells activation-induced apoptosis is used. The parameters of this model are identified by using clinical data generated by monitoring patients starting Highly Active Anti-Retroviral Therapy (HAART). The sampling of blood tests is performed to satisfy the constraints of dynamical system parameter identification. The apoptosis parameter, which is inferred from clinical data, is then shown to play a key role in the early diagnosis of immunological failure.
Published: 2009
Full Text: View/download PDF

7. Evaluation of the presence of equine viral herpesvirus 1 (EHV-1) and equine viral herpesvirus 4 (EHV-4) DNA in stallion semen using polymerase chain reaction (PCR)

Author: Anne Léauté, Chantal Thorin, Stéphan Zientara, Bernard Besse, Fabien Miszczak, Francis Fieni, J.F. Bruyas, Imen Hebia-Fellah, Guillaume Fortier, Bénédicte Ferry, Stéphane Pronost, Berthe-Marie Imbert-Marcille, J.L. Pellerin, Ecole Nationale Vétérinaire de Nantes, Virologie, École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence Française de Sécurité Sanitaire des Aliments (AFSSA), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire Départemental du Calvados - Frank Duncombe, Partenaires INRAE, and Haras Nationaux
Subjects: Male, endocrine system, EQUINE HERPESVIRUS 4, RHINOPNEUMONITIS, 040301 veterinary sciences, viruses, medicine.medical_treatment, Equine herpesvirus 1, POLYMERASE CHAIN REACTION, Semen, STALLION, Breeding, Insemination, EQUINE HERPESVIRUS 1, Virus, law.invention, 0403 veterinary science, 03 medical and health sciences, Food Animals, law, medicine, Animals, FERTILITY, Horses, SEMEN, Small Animals, Polymerase chain reaction, 030304 developmental biology, Cryopreservation, 0303 health sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, urogenital system, Equine, Artificial insemination, 04 agricultural and veterinary sciences, biology.organism_classification, Sperm, Virology, 3. Good health, Cold Temperature, DNA, Viral, Animal Science and Zoology, Equine herpesvirus, Herpesvirus 4, Equid, Herpesvirus 1, Equid, Semen Preservation
Abstract: International audience; In the horse, the risk of,excretion of two major equine pathogens (equine herpesvirus types 1 (EHV-1) and 4 (EHV-4,)) in semen is unknown. The objective of our study was to assess the possible risks for the horizontal transmission of equine rhinopneumonitis herpesviruses via the semen and the effect of the viruses on stallion fertility. Samples of stallion semen (n = 390) were gathered from several different sources. Examination of the semen involved the detection of viral DNA using specific PCR. The mean fertility of the stallions whose sperm tested positive for viral DNA and the mean fertility of stallions whose sperm did not contain viral DNA, were compared using the Student's t-test. EHV-4 viral DNA was not detected in any of the semen samples. EHV-1 DNA was identified in 51 of the 390 samples, (13%). One hundred and eighty-two samples came front 6 studs and there was significant difference (p < 0.05) among the proportion of stallions whose semen tested positive for viral DNA from 0 to 55% between the studs. There was a significant difference (p < 0.014) between the fertility of stallions whose semen tested positive for viral DNA and those whose semen was free from viral DNA. The stallions that excreted the EHV-1 virus in their semen appeared to be more fertile than the non-excretors, but this difference was in fact related to the breeding technique since higher proportion of excretors were found among those whose semen was used fresh rather than preserved by cooling or freezing. In conclusion, this study suggests that the EHV-1 virus may be transmitted via the semen at mating or by artificial insemination as demonstrated with other herpes viruses in other species.
Published: 2009
Full Text: View/download PDF

8. Phenotypic and Functional Analyses of KIR3DL1+ and KIR3DS1+ NK Cell Subsets Demonstrate Differential Regulation by Bw4 Molecules and Induced KIR3DS1 Expression on Stimulated NK Cells

Author: Jean-Denis Bignon, Gilles Folléa, Katia Gagne, Christelle Retière, Nolwenn Kerdudou, Catherine Willem, Véronique Sébille, Gaëlle David, Maelig G. Morvan, Université de Nantes (UN), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Etablissement Français du Sang [Nantes], and GAGNE, Katia
Subjects: Cytotoxicity, Immunologic, Receptors, KIR3DS1, MFI, polyinosinic-polycytidylic acid, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, mean channel fluorescence intensity, Biology, Lymphocyte Activation, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, T-Lymphocyte Subsets, Humans, Immunology and Allergy, Cell Proliferation, 030304 developmental biology, killer-Ig like receptor, 0303 health sciences, Lymphokine-activated killer cell, Cell growth, Janus kinase 3, Receptors, KIR3DL1, poly(IC), Natural killer T cell, KIR, Cell biology, Gene Expression Regulation, HLA-B Antigens, Cell culture, Interleukin 12, Myeloid-derived Suppressor Cell, Natural Killer T-Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, K562 Cells, 030215 immunology
Abstract: Recently, the Z27 mAb was shown to recognize the NK cell-activating receptor KIR3DS1, and several genetic studies suggest that the most probable ligands of KIR3DS1 are HLA class I molecules with the Bw4 motif. Despite these findings, the attempts to establish a functional interaction between KIR3DS1 and its potential ligand have been unsuccessful. Here, we study the proliferation and cytotoxicity of KIR3DS1+ NK cells, compared with KIR3DL1+ NK cells, according to the Bw4+ or Bw4− allogeneic environment. Our results show for the first time that KIR3DS1 expression on NK cells can be induced after exposure to stimulator cells (221, K562, EBV-B cell lines, and B cells), polyinosinic-polycytidylic acid, IL-15, or IL-2. Furthermore, whereas KIR3DL1+ NK cell proliferation and cytotoxicity were inhibited in a Bw4+ but not a Bw4− context, KIR3DS1+ NK cell functions were not influenced by the presence of Bw4 on target cells. Nevertheless, despite the absence of demonstrated regulation of KIR3DS1+ NK cell functions by HLA-Bw4 molecules, we found a higher KIR3DS1+ NK cell frequency and higher levels of KIR3DS1 expression in Bw4+ compared with Bw4− individuals. Altogether, these results suggest that KIR3DS1 does not recognize HLA-Bw4 molecules in a physiological context, and they highlight the induced expression of KIR3DS1 observed on stimulated NK cells and the higher frequency of KIR3DS1+ NK cells in Bw4+ individuals. Because a protective KIR3DS1-Bw4 association has been reported in viral infections, our results further the understanding of the role of KIR3DS1+ NK cells in controlling viral infections.
Published: 2009
Full Text: View/download PDF

9. Natural killer cell licensing after double cord blood transplantation is driven by the self-HLA class I molecules from the dominant cord blood

Author: Hélène Moins-Teisserenc, Antoine Toubert, Jean-Michel Cayuela, Katia Gagne, Pascale Loiseau, Nicolas Dulphy, Eliane Gluckman, Nicolas Guillaume, Régis Peffault de Latour, Guylaine Henry, Gérard Socié, Christelle Retière, Marie Robin, HEMATIM - Hématopoïèse et immunologie - UR UPJV 4666 (HEMATIM), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de la Santé et de la Recherche Médicale (INSERM), Alloimmunité-Autoimmunité-Transplantation (A2T), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université de Paris (UP), Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], Etablissement Français du Sang [Nantes], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), Laboratoire d'Hématologie [CHU Amiens], CHU Amiens-Picardie, Recherche clinique appliquée à l'hématologie ((EA_3518)), Université Paris Diderot - Paris 7 (UPD7), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Immunologie et d'Histocompatibilité, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Eurocord [AP-HP Hôpital Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Diderot - Paris 7 (UPD7), Dulphy, Nicolas, Université Paris Cité (UPCité), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Adult, Male, chemical and pharmacologic phenomena, Cord Blood Stem Cell Transplantation, Immunogenetics, Human leukocyte antigen, HLA-C Antigens, Biology, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Natural killer cell, 03 medical and health sciences, medicine, Humans, Receptor, Online Only Articles, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Cord blood transplantation, ComputingMilieux_MISCELLANEOUS, 4. Education, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Natural killer T cell, Allografts, Hematologic Diseases, Killer Cells, Natural, 030104 developmental biology, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Cord blood, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Immunology, Female, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
Abstract: Natural killer (NK) cells gain functionality through an educational process (“licensing”) that depends on killer immunoglobulin-like receptor (KIR) recognition of self-HLA class I molecules. In allogenic double umbilical cord blood stem cell transplantation (2CBT), the respective roles of the
Published: 2016
Full Text: View/download PDF

10. MICA Mutant A5.1 Influences BK Polyomavirus Reactivation and Associated Nephropathy After Kidney Transplantation

Author: Nathalie Gérard, Béatrice Charreau, Anne Cesbron-Gautier, Simon Mazalrey, Mary-Luce Cheneau, Céline Bressollette-Bodin, Pierre-Jean Gavlovsky, Pierre Tonnerre, Maryvonne Hourmant, Karine Renaudin, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), LabEx TRANSPLANTEX [CHU de Nantes], LabEx IGO 'Immunotherapy, Graft, Oncology' [Nantes], Centre européen des sciences de la transplantation et de l'immunologie [CHU Nantes] (IHU CESTI), Centre hospitalier universitaire de Nantes (CHU Nantes)-Institut de transplantation urologie-néphrologie (ITUN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Etablissement Français du Sang [Nantes], Service d’Anatomopathologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Virologie [CHU Nantes], IHU-Cesti, LabEx IGO, and LabEx Transplantex projects, Nantes Metropole and the Pays de la Loire Region (support to the IHU-Cesti project), the Fondation Centaure (support to the French Transplantation Research Network), the Agence de la Biomédecine and the IHU-Cesti., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010), LabEX IGO Immunothérapie Grand Ouest, Nantes Université (Nantes Univ), Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, and Initiative d'excellence - Par-delà les frontières, l'Université de Strasbourg - - UNISTRA2010 - ANR-10-IDEX-0002 - IDEX - VALID
Subjects: 0301 basic medicine, Adult, Male, BK polyomavirus, 030230 surgery, Biology, Major histocompatibility complex, medicine.disease_cause, MICA polymorphism, Nephropathy, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Immunology and Allergy, Humans, innate immunity, Kidney transplantation, Aged, Retrospective Studies, Aged, 80 and over, Polyomavirus Infections, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Nephritis, Histocompatibility Antigens Class I, Middle Aged, medicine.disease, Virology, Kidney Transplantation, 3. Good health, Transplant rejection, BK virus, MICA A51 mutation, Transplantation, stomatognathic diseases, 030104 developmental biology, Infectious Diseases, BK Virus, Immunology, Mutation, biology.protein, Female, Virus Activation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Immunosuppressive Agents
Abstract: International audience; Background. BK polyomavirus (BKPyV) frequently reactivates in kidney transplant recipients during immunosuppressive therapy and triggers BKPyV-associated nephropathy and graft rejection. Determining effective risk factors for BKPyV reactivation is required to achieve efficient prevention.Methods. This study investigated the role of major histocompatibility complex (MHC) class I-related chain A (MICA) in BKPyV reactivation in a cohort of 144 transplant donor/recipient pairs, including recipients with no reactivation (controllers) and those with mild (virurics) or severe (viremics) BKPyV reactivation after graft receipt.Results. We show that, in the kidney, MICA is predominantly expressed in tubule epithelial cells, the natural targets of BKPyV, questioning a role for MICA in the immune control of BKPyV infection. Focusing on MICA genotype, we found a lower incidence of BKPyV reactivation in recipients of a renal graft from a donor carrying the MICA A5.1 mutant, which encodes a truncated nonconventional MICA. We established that a mismatch for MICA A5.1 between transplant donor and recipient is critical for BKPyV reactivation and BKPyV-associated nephropathy. Functionally, we found that a low prevalence of BKPyV reactivation was associated with elevated anti-MICA sensitization and reduced plasma level of soluble MICA in recipients, 2 potential effector mechanisms.Discussions. These findings identify the MHC-related MICA as an immunogenetic factor that may functionally influence anti-BKPyV immune responses and infection outcomes.
Published: 2016
Full Text: View/download PDF

11. Cytomegalovirus-Infected Primary Endothelial Cells Trigger NKG2C+ Natural Killer Cells

Author: Djaoud, Zakia, Riou, Raphaëlle, Gavlovsky, Pierre-Jean, Mehlal, Souad, Bressollette, Céline, Gérard, Nathalie, Gagne, Katia, Charreau, Béatrice, Retière, Christelle, Le Bihan, Sylvie, Instituts Hospitalo-Universitaires B - Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU) - - CESTI (TSI-IHU)2010 - ANR-10-IBHU-0005 - IBHU - VALID, Laboratoires d'excellence - Immunothérapies Grand Ouest - - IGO2011 - ANR-11-LABX-0016 - LABX - VALID, Initiative d'excellence - Par-delà les frontières, l'Université de Strasbourg - - UNISTRA2010 - ANR-10-IDEX-0002 - IDEX - VALID, Etablissement Français du Sang [Nantes], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), 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), The EFS Pays de la Loire, Leucémie Espoir Atlantique Famille (LEAF) and by grants from the ‘Etablissement Français du Sang 2010-06’ and NAGMO, a CIFRE grant (No. 447/2011), the Région des Pays de la Loire (ARMINA project), the Nantes metropole, the ‘Fondation Centaure’ (RTRS)., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-LABX-0016,IGO,Immunothérapies Grand Ouest(2011), and ANR-10-IDEX-0002,UNISTRA,Par-delà les frontières, l'Université de Strasbourg(2010)
Subjects: [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, KG2C, Human leukocyte antigen E, Endothelial cells, Histocompatibility Antigens Class I, virus diseases, Cytomegalovirus, Dendritic Cells, Fibroblasts, Lymphocyte Activation, Cell Degranulation, Lymphocyte Subsets, Killer Cells, Natural, Cytomegalovirus Infections, Receptors, KIR2DL1, Natural killer cells, Humans, Endothelium, Vascular, NK Cell Lectin-Like Receptor Subfamily C, Immunologic Memory, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Aorta, Cells, Cultured, Cell Proliferation
Abstract: International audience; Among innate cells, natural killer (NK) cells play a crucial role in the defense against cytomegalovirus (CMV). In some individuals, CMV infection induces the expansion of NKG2C+ NK cells that persist after control of the infection. We have previously shown that KIR2DL+ NK cells, in contrast to NKG2C+ NK cells, contribute to controlling CMV infection using a CMVinfected monocyte-derived dendritic cell (MDDC) model. However, the nature of CMV-infected cells contributing to the expansion of the NKG2C+ NK cell subset remains unclear. To gain more insight into this question, we investigated the contribution of NKG2C+ NK cell activation by CMV-infected primary human aortic endothelial cells (EC) isolated from kidney transplant donors, which constitutively express the human leukocyte antigen (HLA)-E molecule. Here, we show that, although classic HLA class I expression was drastically downregulated, nonclassic HLA-E expression was maintained in CMV-infected EC. By comparing HLA expression patterns in CMV-infected EC, fibroblasts and MDDC, we demonstrate a cell-dependent modulation of HLA-E expression by CMV infection. NKG2C+ NK cell degranulation was significantly triggered by CMV-infected EC regardless of the nature of the HLA-E allele product. EC, predominantly present in vessels, may constitute a privileged site for CMV infection that drives a ‘memory’ NKG2C+ NK cell subset.
Published: 2015
Full Text: View/download PDF

12. Use of killer cell immunoglobulin-like receptor genes as early markers of hematopoietic chimerism after double-umbilical cord blood transplantation

Author: Nolwenn Legrand, Katia Gagne, Anne Cesbron, Catherine Willem, Patrice Chevallier, Pauline Rettman, Laurence Lodé, Christelle Retière, David Senitzer, Etablissement Français du Sang [Nantes], Université de Nantes (UN), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hôtel-Dieu de Nantes, LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), City of Hope Medical Center [Duarte, CA, USA] (HLA laboratory), and RETIERE, Christelle
Subjects: Male, KIR genes, [SDV]Life Sciences [q-bio], Killer-cell immunoglobulin-like receptor, markers, Cord Blood Stem Cell Transplantation, Transplantation Chimera, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Receptors, KIR, Medicine, Humans, Online Only Articles, Gene, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, killer cell immunoglobulin-like receptor genes, 0303 health sciences, Umbilical Cord Blood Transplantation, business.industry, umbilical cord blood transplantation, Hematology, Recovery of Function, 3. Good health, [SDV] Life Sciences [q-bio], Haematopoiesis, chimerism, Immunology, Female, business, DISEASE RELAPSE, Biomarkers, 030215 immunology
Abstract: It has been established that hematopoietic chimerism after double umbilical cord blood transplantation (dUCBT) can predict disease relapse and detect potential engraftment failure.[1][1]–[3][2] The use of a precise method to evaluate residual host hematopoiesis is imperative because it has been
Published: 2015
Full Text: View/download PDF

13. Role of IL-12 in overcoming the low responsiveness of NK cells to missing self after traumatic brain injury

Author: Mickael Vourc'h, Karim Asehnoune, Raphaël Cinotti, Bertrand Rozec, Antoine Roquilly, Hélène Morin, Christelle Retière, Gaëlle David, RETIERE, Christelle, Centre hospitalier universitaire de Nantes (CHU Nantes), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Etablissement Français du Sang [Nantes], and Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826)
Subjects: 0301 basic medicine, Adult, Male, Traumatic brain injury, [SDV]Life Sciences [q-bio], Immunology, Cell, Genes, MHC Class II, Genes, MHC Class I, Stimulation, Human leukocyte antigen, NK cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Monocytes, Cell Degranulation, 03 medical and health sciences, Interferon-gamma, Young Adult, 0302 clinical medicine, Immune suppression, Brain Injuries, Traumatic, medicine, Immunology and Allergy, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Aged, Antibody-dependent cell-mediated cytotoxicity, Aged, 80 and over, business.industry, Degranulation, HLA class I, Middle Aged, medicine.disease, Phenotype, Interleukin-12, 3. Good health, KIR, [SDV] Life Sciences [q-bio], Killer Cells, Natural, 030104 developmental biology, medicine.anatomical_structure, IL-12, Interleukin 12, Female, business, 030215 immunology
Abstract: International audience; Blood samples from 32 patients with severe Traumatic brain injury (TBI) were studied and compared with 11 cardiac surgery patients, and 29 healthy controls. A dramatic decreased expression of HLA class I molecules on monocytes was associated with increased KIR+ NK cell frequency in TBI patients. Overall, the phenotype of TBI NK cells marked by KIR and CD57 expression and lower level of NKp46 and DNAM-1 reflected a differentiated state. The NK-cell response to missing self was marked by lower degranulation and lower IFN-γ production after stimulation with HLA class I deficient cell line. In contrast, the NK-cell ADCC was not altered. IL-12 was able to restore both IFN-γ production and the cytotoxicity capacities of NK cells. This study provides the first extensive description of the phenotype and functions of NK cells in TBI patients. Further evaluation of IL-12 treatment to overcome immunosuppression-induced nosocomial infections is warranted.
Published: 2015
Full Text: View/download PDF

14. Influence of patients' characteristics and disease management on asthma control

Author: S. Chretin, Eric Van Ganse, Yves Pacheco, Laurent Laforest, Geneviève Chamba, Jean Bousquet, Gilles Devouassoux, Gisele Bauguil, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, laboratoire du sommeil, CHU Grenoble, Service des maladies respiratoires, Hospices Civils de Lyon (HCL), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Male, Adult, medicine.medical_specialty, Adolescent, Immunology, Pharmacy, Lower risk, primary care, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Drug Therapy, Internal medicine, Control, medicine, sex, Humans, Immunology and Allergy, Anti-Asthmatic Agents, 030212 general & internal medicine, Disease management (health), Medical prescription, Retrospective Studies, Asthma, Observer Variation, 2. Zero hunger, therapy, business.industry, Smoking, Disease Management, Retrospective cohort study, Odds ratio, Middle Aged, medicine.disease, 3. Good health, Logistic Models, 030228 respiratory system, Multivariate Analysis, Combination, Physical therapy, Regression Analysis, Drug Therapy, Combination, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index
Abstract: International audience; BACKGROUND: Although asthma control is a major outcome in disease management, little is known about its determinants. OBJECTIVES: We sought to study the relationships between asthma control and patient characteristics or asthma management. METHODS: Asthmatic patients (age 18-50 years) who were regular customers of pharmacies and had a prescription for an antiasthma medication were recruited consecutively. Patients completed a questionnaire, which was complemented by computerized pharmacy records of previously dispensed medications. Asthma control (adequate/inadequate) was assessed with the Asthma Control Test. Determinants of asthma control were identified by means of multivariate logistic regression analysis. RESULTS: The mean age of the 1351 patients included was 36.8 years (SD, 9.8), and 55.8% were women. A minority of patients were considered to have had their symptoms adequately controlled. Smoking, female sex, and a body mass index of greater than 30 kg/m2 were all independent determinants of inadequate control. Compared with patients receiving inhaled corticosteroid monotherapy, those who were dispensed fixed combinations of inhaled corticosteroids and long-acting beta-agonists presented with a significantly lower risk of inadequate asthma control (odds ratio, 0.58; 95% CI, 0.35-0.96). CONCLUSION: Asthma control varied according to both the patients' characteristics and therapy. CLINICAL IMPLICATIONS: Our results strongly support the need to improve asthma control, especially in primary care and in women. A regular use of fixed controller combinations, helping patients to quit smoking, or addressing weight issues might contribute to improvement in asthma control.
Published: 2006
Full Text: View/download PDF

15. Increased IGM and IGG anti-NEU5GC antibodies in infectious mononucleosis (IMN): link with multiple sclerosis (MS)?

Author: Le Berre, Ludmilla, Salama, Apolline, Evanno, Gwénaëlle, Rousse, Juliette, Nicot, Arnaud, Semana, Gilbert, Laplaud, David A., Imbert, Berthe-Marie, Drouet, Emmanuel, Soulillou, Jean-Paul, Jonchère, Laurent, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Microenvironnement et cancer (MiCa), Université de Rennes (UR)-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 ), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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 ), and Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF)
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: International audience; Introduction: Multiple Sclerosis (MS) is a chronic inflammatory and demyelinating disease which displays an autoimmune component at its overt clinical stage. Among etiological hypotheses, the potential initiating role of EBV in the disease has been raised following works linking EBNA levels and the risk of MS occurrence [1] showing a linkage between the occurrence of IMN and MS. Our hypothesis is that a vigorous production of anti-Neu5Gc in IMN (as indirectly measured by Paul-Bunnell Davidson reaction) may induce brain blood barrier alterations when the EBV primo-infection is contemporary of an extraordinary high frequency of EBV committed T cells and of circulating EBV+ memory B cells[2]. Our aim was to measure anti-Neu5Gc IgG and IgM levels during the IMN and to investigate whether levels of anti-NeuGc could be also increased in MS. Material and Methods: Sera from 49 patients with overt IMN were collected from the University Hospital of Grenoble and Nantes. The gender ratio was 22F/ 27M. The age average was 24 years (range: 7- 65). Two cohorts of EBV negative individuals (n= 45) and healthy individuals (n= 120) were used as controls. A second cohort of 46 patients with proven MS was collected from the University Hospital of Nantes. The gender ratio was 30F/ 16M. The age average was 48 years (range: 22-73). This cohort contained 30 patients presenting a Remitting Relapsing (RR) form (65.2%) and 16 with a Secondary or Primary Progressive (SP-PP) one (34.7%). A cohort of healthy individuals (n= 37) matched for gender and age was used as controls. On these samples, we performed two Elisa [3][4] to quantify anti-Neu5Gc IgG and IgM antibodies. Results: We showed a highly significant increase in anti-Neu5Gc IgM in IMN patients in comparison to EBV negative controls (0.82±0.16 vs. 0.15±0.05 ng/ul; p
Published: 2015

16. Human herpesvirus 6 reactivation before engraftment is strongly predictive of graft failure after double umbilical cord blood allogeneic stem cell transplantation in adults

Author: Philippe Moreau, Myriam Labopin, Laurence Lodé, Patrice Chevallier, Sophie Derenne, Pierre Peterlin, Jacques Delaunay, Katia Gagne, Benoit Tessoulin, Berthe-Marie Imbert-Marcille, Steven Le Gouill, Thierry Guillaume, Mohamad Mohty, Marina Illiaquer, Patricia Herry, Florent Malard, Amandine Le Bourgeois, Yohann Foucher, Sameh Ayari, Anne Cesbron, Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Nantes (UN), 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), Unité d’Ingénierie Cellulaire [EFS, Nantes], EFS Centre-Pays de la Loire [Nantes], Etablissement Français du Sang [Pays de la Loire] (EFS Pays de la Loire), EFS, Etablissement Français du Sang [Nantes], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Centre hospitalier universitaire de Nantes (CHU Nantes), GAGNE, Katia, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service d'Hématologie Clinique [CHU Nantes] (Unité d'Investigation Clinique), Biostatistique, Pharmaco-Epidémiologie et Recherche en Sciences Humaines [UNIV Nantes], Laboratoire d'Histocompatibilité et d'Immunogénétique [EFS Nantes], Département d'hématologie et de biologie [CHU Nantes], Service de virologie [CHU Nantes], and Le Bihan, Sylvie
Subjects: Graft Rejection, Male, Cancer Research, Herpesvirus 6, Human, Graft vs Host Disease, Umbilical cord, Gastroenterology, 0302 clinical medicine, Recurrence, Risk Factors, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Histocompatibility Testing, Hazard ratio, Age Factors, Hematology, Middle Aged, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Hematologic Neoplasms, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Cord Blood Stem Cell Transplantation, Adult, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Adolescent, Roseolovirus Infections, ABO Blood-Group System, 03 medical and health sciences, Young Adult, ABO blood group system, Internal medicine, Genetics, medicine, Humans, Transplantation, Homologous, Molecular Biology, Survival analysis, Aged, Retrospective Studies, business.industry, Cell Biology, Odds ratio, Survival Analysis, Confidence interval, Surgery, Transplantation, Virus Activation, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; Our main objective was to determine new factors associated with engraftment and single-unit predominance after double umbilical cord blood (UCB) allogeneic stem-cell transplantation. Engraftment occurred in 78% of cases in this retrospective study including 77 adult patients. Three-year overall survival, disease-free survival, relapse incidence, and nonrelapse mortality were 55 ± 6%, 44 ± 6%, 33 ± 5%, and 23 ± 4%, respectively. In multivariate analysis, Human herpesvirus 6 reactivation during aplasia (hazard ratio [HR] = 2.63; 95% confidence interval [CI]: 1.64-4.17; p < 0.001), younger recipient age (
Published: 2014
Full Text: View/download PDF

17. Hydrocortisone Prevents Immunosuppression by Interleukin-10+ Natural Killer Cells After Trauma-Hemorrhage

Author: Mickael Vourc'h, Jocelyne Caillon, Christelle Retière, Jose A Villadangos, Frédéric Altare, Karim Asehnoune, Jean Pierre Segain, Régis Josien, Cédric Jacqueline, Cécile Braudeau, Alexis Broquet, Damien Masson, Antoine Roquilly, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Faculté de Médecine, Intensive Care Unit, Anesthesia and Critical Care Department, Hôpital Hôtel-Dieu de Nantes - Centre Hospitalier Universitaire de Nantes (Hôpital Hôtel-Dieu de Nantes - CHU de Nantes), Biochemistry Department, Physiologie des Adaptations Nutritionnelles (PhAN), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Laboratoire d’Immunologie, Centre d’Immunomonitorage Nantes Atlantique (CIMNA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), 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), Université de Nantes (UN), Immunovirologie et Polymorphisme Génétique, Etablissement Français du Sang Centre-Atlantique, Department of Microbiology and Immunology ,(Doherty Institute of Infection and Immunity), University of Melbourne, Department of Biochemistry and Molecular Biology, Bio21 Institute, Physiologie des Adaptations Nutritionnelles [UMR_A1280] (PhAN), Unité 892, Institut de Recherche Thérapeutique, and Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, medicine.medical_treatment, interleukin-10, Anti-Inflammatory Agents, Stimulation, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Mice, 0302 clinical medicine, Receptor, 0303 health sciences, Cross Infection, Trauma Severity Indices, natural killer cells, Immunosuppression, Middle Aged, Staphylococcal Infections, 3. Good health, Killer Cells, Natural, Interleukin 10, Cytokines, Female, medicine.drug, Adult, Adolescent, chemical and pharmacologic phenomena, Staphylococcal infections, Trauma, 03 medical and health sciences, Young Adult, medicine, Pneumonia, Bacterial, Animals, Humans, pneumonia, dendritic cells, hydrocortisone, 030304 developmental biology, Hydrocortisone, Aged, Dose-Response Relationship, Drug, Septic shock, business.industry, medicine.disease, Pneumonia, Immunology, Wounds and Injuries, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: Trauma induces a state of immunosuppression, which is responsible for the development of nosocomial infections. Hydrocortisone reduces the rate of pneumonia in patients with trauma. Because alterations of dendritic cells and natural killer cells play a central role in trauma-induced immunosuppression, we investigated whether hydrocortisone modulates the dendritic cell/natural killer cell cross talk in the context of posttraumatic pneumonia.Experimental study.Research laboratory from an university hospital.Bagg Albino/cJ mice (weight, 20-24 g).First, in an a priori substudy of a multicenter, randomized, double-blind, placebo-controlled trial of hydrocortisone (200 mg/d for 7 d) in patients with severe trauma, we have measured the blood levels of five cytokines (tumor necrosis factor-α, interleukin-6, interleukin-10, interleukin-12, interleukin-17) at day 1 and day 8. In a second step, the effects of hydrocortisone on dendritic cell/natural killer cell cross talk were studied in a mouse model of posttraumatic pneumonia. Hydrocortisone (0.6 mg/mice i.p.) was administered immediately after hemorrhage. Twenty-four hours later, the mice were challenged with Staphylococcus aureus (7 × 10 colony-forming units).Using sera collected during a multicenter study in patients with trauma, we found that hydrocortisone decreased the blood level of interleukin-10, a cytokine centrally involved in the regulation of dendritic cell/natural killer cell cluster. In a mouse model of trauma-hemorrhage-induced immunosuppression, splenic natural killer cells induced an interleukin-10-dependent elimination of splenic dendritic cell. Hydrocortisone treatment reduced this suppressive function of natural killer cells and increased survival of mice with posthemorrhage pneumonia. The reduction of the interleukin-10 level in natural killer cells by hydrocortisone was partially dependent on the up-regulation of glucocorticoid-induced tumor necrosis factor receptor-ligand (TNFsf18) on dendritic cell.These data demonstrate that trauma-induced immunosuppression is characterized by an interleukin-10-dependent elimination of dendritic cell by natural killer cells and that hydrocortisone improves outcome by limiting this immunosuppressive feedback loop.
Published: 2014
Full Text: View/download PDF

18. Large Spectrum of HLA-C Recognition by Killer Ig–like Receptor (KIR)2DL2 and KIR2DL3 and Restricted C1 Specificity of KIR2DS2: Dominant Impact of KIR2DL2/KIR2DS2 on KIR2D NK Cell Repertoire Formation

Author: Gaëlle David, Catherine Willem, Katia Gagne, Nolwenn Legrand, Zakia Djaoud, Christelle Retière, Anne Cesbron, Pauline Rettman, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Etablissement Français du Sang [Nantes], Université de Nantes (UN), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), and RETIERE, Christelle
Subjects: Genotype, Immunology, Cell, HLA-C Antigens, Human leukocyte antigen, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Lymphocyte Activation, 03 medical and health sciences, HLA-C, Interleukin 21, 0302 clinical medicine, Receptors, KIR, KIR2DL1, medicine, Humans, Immunology and Allergy, 10. No inequality, Receptor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Alleles, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Lymphokine-activated killer cell, Repertoire, Cell biology, Killer Cells, Natural, medicine.anatomical_structure, Receptors, KIR2DL3, Receptors, KIR2DL2, Receptors, KIR2DL1, 030215 immunology
Abstract: The interactions of killer Ig–like receptor 2D (KIR2D) with HLA-C ligands contribute to functional NK cell education and regulate NK cell functions. Although simple alloreactive rules have been established for inhibitory KIR2DL, those governing activating KIR2DS function are still undefined, and those governing the formation of the KIR2D repertoire are still debated. In this study, we investigated the specificity of KIR2DL1/2/3 and KIR2DS1/2, dissected each KIR2D function, and assessed the impact of revisited specificities on the KIR2D NK cell repertoire formation from a large cohort of 159 KIR and HLA genotyped individuals. We report that KIR2DL2+ and KIR2DL3+ NK cells reacted similarly against HLA-C+ target cells, irrespective of C1 or C2 allele expression. In contrast, KIR2DL1+ NK cells specifically reacted against C2 alleles, suggesting a larger spectrum of HLA-C recognition by KIR2DL2 and KIR2DL3 than KIR2DL1. KIR2DS2+ KIR2DL2− NK cell clones were C1-reactive irrespective of their HLA-C environment. However, when KIR2DS2 and KIR2DL2 were coexpressed, NK cell inhibition via KIR2DL2 overrode NK cell activation via KIR2DS2. In contrast, KIR2DL1 and KIR2DS2 had an additive enhancing effect on NK cell responses against C1C1 target cells. KIR2DL2/3/S2 NK cells predominated within the KIR repertoire in KIR2DL2/S2+ individuals. In contrast, the KIR2DL1/S1 NK cell compartment is dominant in C2C2 KIR2DL2/S2− individuals. Moreover, our results suggest that together with KIR2DL2, activating KIR2DS1 and KIR2DS2 expression limits KIR2DL1 acquisition on NK cells. Altogether, our results suggest that the NK cell repertoire is remolded by the activating and inhibitory KIR2D and their cognate ligands.
Published: 2013
Full Text: View/download PDF

19. Herpesvirus detection and cytokine levels (IL-10, IL-6, and IFN-gamma) in ocular fluid from tunisian immunocompetent patients with uveitis

Author: Nahdi, I., Abdelwahed, R. B., Boukoum, H., Bressollette-Bodin, C., Attia, S., Yahia, S. B., Fisson, S., Khairallah, M., Aouni, M., Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche et d'Application en Traitement de l'Image et du Signal (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunologie moléculaire et biothérapies innovantes (IMBI), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Centro Internacional de Mejoramiento de Maïs y Trigo, Partenaires INRAE, Université de Monastir - University of Monastir (UM), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École Supérieure Chimie Physique Électronique de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and École pratique des hautes études (EPHE)
Subjects: Adult, Aged, 80 and over, Male, Tunisia, Adolescent, viruses, [SDV]Life Sciences [q-bio], virus diseases, Herpesviridae Infections, Middle Aged, Aqueous Humor, Uveitis, Young Adult, DNA, Viral, Prevalence, Cytokines, Humans, Female, Herpesviridae, Aged
Abstract: International audience; Human herpesviruses (HHVs) are involved in the pathogenesis of different types of uveitis. Cytokine response plays an important role in virus-induced immunopathology. This study aimed to investigate the incidence of HHVs in aqueous humor samples of immunocompetent patients with suspected viral uveitis and cytokine (IL-10, IL-6, and IFN-gamma) expression profiling. Forty-seven aqueous humor samples were collected from immunocompetent patients with viral uveitis. Samples were assayed for HHV-1 to HHV-8 by in-house real-time polymerase chain reactions. IL-6, IL-10, and IFN-gamma were quantified with a cytometric bead array. Relations between viral detection, cytokine profiles, and clinical data were studied. At least one viral genome was detected in 21 aqueous humor samples analyzed. Varicella-zoster virus (VZV) was detected in 14 of the positive samples, cytomegalovirus (CMV) in 8, HSV-1 in 1, Epstein-Barr virus (EBV) in 4, and HHV-6 in 2. More than one viral genome was detected in seven aqueous humor samples. Aqueous humor samples positive for HHV-DNA contained significant levels of IL-6, IL-10, and IFN-gamma, compared to HHV-DNA negative samples. High levels of IL-6 were detected in patients with CMV-DNA in their aqueous humor samples. Significantly higher levels of IL-10 and IFN-gamma were found in positive samples for VZV, EBV, and HHV-6 DNA than in negative aqueous humor ones. VZV was the principal etiologic agent of uveitis in this Tunisian series, with CMV the second most common agent. Knowledge of immunoregulatory interactions and dynamic changes in viral uveitis may be a key to understand the pathogenesis leading to more-effective treatments. J. Med. Virol. 9999:1-8, 2013. (c) 2013 Wiley Periodicals, Inc.
Published: 2013
Full Text: View/download PDF

20. Amplified NKG2C+ NK cells in cytomegalovirus (CMV) infection preferentially express killer cell Ig-like receptor 2DL: functional impact in controlling CMV-infected dendritic cells

Author: Gaëlle David, Christelle Retière, Nolwenn Legrand, Souad Mehlal, Katia Gagne, Céline Bressollette, Anne Cesbron, Pauline Rettman, Catherine Willem, Zakia Djaoud, Berthe-Marie Imbert-Marcille, Etablissement Français du Sang [Nantes], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Université de Nantes (UN), LabEx Transplantex [Strasbourg], Université de Strasbourg (UNISTRA), and RETIERE, Christelle
Subjects: Immunology, Cell, Population, Human leukocyte antigen, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, Immune system, KIR2DL1, Receptors, KIR, medicine, Immunology and Allergy, Humans, education, Receptor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, 0303 health sciences, education.field_of_study, Histocompatibility Antigens Class I, virus diseases, Dendritic Cells, Flow Cytometry, Virology, Lymphocyte Subsets, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, Receptors, KIR2DL3, Cytomegalovirus Infections, Receptors, KIR2DL1, NK Cell Lectin-Like Receptor Subfamily C, 030215 immunology
Abstract: CMV infection represents a major complication in hematopoietic stem cell transplantation, which compromises graft outcome. Downregulation of HLA class I expression is one mechanism by which CMV evades T cell–mediated immune detection, rendering infected cells vulnerable to killer cell Ig-like receptor (KIR)+ NK cells. In this study, we observed that the amplified NKG2C+ NK cell population observed specifically in CMV seropositive individuals mainly expressed KIR2DL receptors. We have shown that HLA class I expression was downregulated on CMV-infected immature dendritic cells (iDCs), which escape to HLA-A2-pp65–specific T lymphocytes but strongly trigger the degranulation of KIR2D+ NK cells. CMV infection conferred a vulnerability of C2C2+ iDCs to educated KIR2DL1+ and KIR2DL3+ NK cell subsets. Alloreactivity of KIR2DL1+ NK cell subsets against C1C1+ iDCs was maintained independently of CMV infection. Unexpectedly, CMV-infected C1C1+ iDCs did not activate KIR2DL3+ NK cell reactivity, suggesting a potential CMV evasion to KIR2DL3 NK cell recognition. Altogether, the coexpression of KIR and NKG2C on expanded NK cell subsets could be related to a functional contribution of KIR in CMV infection and should be investigated in hematopoietic stem cell transplantation, in which the beneficial impact of CMV infection has been reported on the graft-versus-leukemia effect.
Published: 2013
Full Text: View/download PDF

21. Neutrophil gelatinase-associated lipocalin, a marker of tubular dysfunction, is not increased in long-term virologically controlled patients receiving a tenofovir/emtricitabine + nevirapine regimen

Author: Solène Secher, K. Bach-Ngohou, François Raffi, F. Fakhouri, Clotilde Allavena, Eric Billaud, T. Dejoie, Véronique Reliquet, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire de Biochimie [CHU Nantes], COREVIH Pays Loire, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), and Le Bihan, Sylvie
Subjects: Male, 030232 urology & nephrology, HIV Infections, Gastroenterology, Deoxycytidine, 0302 clinical medicine, Abacavir, Emtricitabine, Pharmacology (medical), 030212 general & internal medicine, NGAL, renal toxicity, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Acute kidney injury, virus diseases, Lamivudine, Middle Aged, Lipocalins, 3. Good health, Infectious Diseases, nucleoside analogues, Female, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Nevirapine, Anti-HIV Agents, Urinary system, Population, Organophosphonates, 03 medical and health sciences, Lipocalin-2, Internal medicine, Proto-Oncogene Proteins, medicine, Humans, education, Tenofovir, Pharmacology, business.industry, Adenine, HIV infection, medicine.disease, Endocrinology, Cross-Sectional Studies, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease, Acute-Phase Proteins
Abstract: International audience; OBJECTIVES: Tenofovir may be associated with nephrotoxicity. Several studies have shown that an early increase in urinary neutrophil gelatinase-associated lipocalin (NGAL) may predict the occurrence of acute kidney injury. We investigated urine and plasma NGAL in patients on long-term treatment with nevirapine associated with either tenofovir/emtricitabine or abacavir/lamivudine.PATIENTS AND METHODS: We studied 40 virologically controlled Caucasian patients on stable treatment (median >4 years) with tenofovir/emtricitabine + nevirapine (n = 20) or abacavir/lamivudine + nevirapine (n = 20), and no history of kidney disease, high blood pressure or diabetes. Plasma immunovirological parameters (NGAL and C-reactive protein) and urinary NGAL, β2-microglobulin and α1-microglobulin were measured during a routine clinical visit.RESULTS: Median concentrations of NGAL were in the normal range, but were significantly higher in the abacavir/lamivudine group compared with the tenofovir/emtricitabine group both in the plasma, at 74.9 and 66.0 ng/mL (P = 0.032), respectively, and in the urine, at 36.1 and 12.8 ng/mL (P = 0.017), respectively.CONCLUSIONS: Plasma and urinary NGAL concentrations remained in the normal range in this long-term virologically controlld population without any overt renal disease. The usefulness of NGAL in detecting sub-clinical renal dysfunction appears to be very limited.
Published: 2013
Full Text: View/download PDF

22. Genome-Wide Analysis of Host mRNA Translation during Hepatitis C Virus Infection

Author: Céline Hernandez, Stéphan Vagner, Cyrille Feray, Audrey Bihouée, Rémi Houlgatte, Sandra Pierredon, Catherine Le Berre-Scoul, Arielle R. Rosenberg, Hélène Colman, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Virologie de l'hépatite C (EA 4474), Université Paris Descartes - Paris 5 (UPD5), Institut Claudius Regaud, Plateforme Puces à ADN-OGP, Université de Nantes (UN), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and UL, NGERE
Subjects: 0303 health sciences, Microarray analysis techniques, [SDV]Life Sciences [q-bio], Immunology, virus diseases, Biology, Microbiology, Molecular biology, Ribosome, digestive system diseases, 3. Good health, NS2-3 protease, Transcriptome, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Viral replication, Virology, Insect Science, Translational regulation, Protein biosynthesis, 030211 gastroenterology & hepatology, Gene, 030304 developmental biology
Abstract: In the model of Huh-7.5.1 hepatocyte cells infected by the JFH1 hepatitis C virus (HCV) strain, transcriptomic and proteomic studies have revealed modulations of pathways governing mainly apoptosis and cell cycling. Differences between transcriptomic and proteomic studies pointed to regulations occurring at the posttranscriptional level, including the control of mRNA translation. In this study, we investigated at the genome-wide level the translational regulation occurring during HCV infection. Sucrose gradient ultracentrifugation followed by microarray analysis was used to identify translationally regulated mRNAs (mRNAs associated with ribosomes) from JFH1-infected and uninfected Huh-7.5.1 cells. Translationally regulated mRNAs were found to correspond to genes enriched in specific pathways, including vesicular transport and posttranscriptional regulation. Interestingly, the strongest translational regulation was found for mRNAs encoding proteins involved in pre-mRNA splicing, mRNA translation, and protein folding. Strikingly, these pathways were not previously identified, through transcriptomic studies, as being modulated following HCV infection. Importantly, the observed changes in host mRNA translation were directly due to HCV replication rather than to HCV entry, since they were not observed in JFH1-infected Huh-7.5.1 cells treated with a potent HCV NS3 protease inhibitor. Overall, this study highlights the need to consider, beyond transcriptomic or proteomic studies, the modulation of host mRNA translation as an important aspect of HCV infection.
Published: 2013
Full Text: View/download PDF

23. Higher risk of death among MEN1 patients with mutations in the JunD interacting domain: a Groupe d'etude des Tumeurs Endocrines (GTE) cohort study

Author: Bruno Vergès, Albert Beckers, Brigitte Delemer, Vincent Rohmer, Arnaud Murat, Jean-Marc Kuhn, Philippe Ruszniewski, Christine Binquet, Julien Thevenon, Philippe Caron, Georges Weryha, Michel Rodier, Sophie Giraud, F. Archambeaud, I. Guilhem, Morgane Le Bras, Philippe Chanson, Béatrice Parfait, Jean-Louis Sadoul, Lionel Groussin, Patricia Niccoli, Catherine Cardot-Bauters, Philippe Bouchard, Eric Baudin, Françoise Duron, Michel Renard, Hélène Bihan, Véronique Kerlan, P. Lecomte, Catherine Lombard-Bohas, Abderrahmane Bourredjem, Anne Barlier, Emilie Castermans, Françoise Borson-Chazot, Bernard Goichot, Olivier Chabre, Antoine Tabarin, Alain Calender, Laurence Faivre, Hélène Du Boullay, Pierre Goudet, Eric Clauser, Alfred Penfornis, Marie-Françoise Odou, Université Joseph Fourier - Grenoble 1 ( UJF ), Immunovirologie et polymorphisme génétique, Université de Nantes ( UN ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Unité Mixte de Génétique Constitutionnelle des Cancers Fréquents, Centre Léon Bérard [Lyon]-Hospices Civils de Lyon ( HCL ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de médecine nucléaire, Fédération d'endocrinologie-Groupement hospitalier Lyon-Est, Centre de recherche en neurobiologie - neurophysiologie de Marseille ( CRN2M ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Service d'Endocrinologie ( BORDEAUX - Endocrino ), CHU Bordeaux [Bordeaux], Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux ( Inserm U745 ), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement ( IFR71 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL ( ENSCP ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut de Recherche pour le Développement ( IRD ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Biologie du Cancer et de l'Infection ( BCI - UMR S1036 ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Grenoble Alpes ( UGA ), Service d'Endocrinologie ( LIEGE - Endocrino ), Université de Liège, Department of Gastroenterology, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Beaujon, Pathologie et virologie moléculaire ( PVM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'Endocrinologie - Diabète - Nutrition [Reims], Université de Reims Champagne-Ardenne ( URCA ) -Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Laboratoire Microorganismes : Génome et Environnement ( LMGE ), Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Hospitalier Universitaire [Rennes], Service d'Endocrinologie ( ANGERS - Endocrino ), CHU Angers, Département de Médecine Interne et Nutrition, CHU Strasbourg, Service d'Endocrinologie ( TOULOUSE - Endocrino ), CHU Toulouse [Toulouse], Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 ( UP11 ) -IFR93-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Gustave Roussy ( IGR ), Médecine nucléaire, Département d'imagerie médicale [Gustave Roussy], Institut Gustave Roussy ( IGR ) -Institut Gustave Roussy ( IGR ), Service d'Endocrinologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service d'Endocrinologie ( TOURS - Endocrino ), CHRU Tours, Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Conservatoire National des Arts et Métiers - Paris ( CNAM Paris ), Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Médecine interne B, Endocrinologie, Diabète, Maladies métaboliques [CHU Limoges], CHU Limoges, Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Service d'Endocrinologie ( CHRU - Endocrino ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Service de Diabétologie, Service des maladies métaboliques et endocriniennes, Hôpital Universitaire Carémeau [Nîmes], Service d'Endocrinologie ( NICE - Endocrino ), CHU Nice, Université Blaise Pascal - Clermont-Ferrand 2 ( UBP ) -Centre National de la Recherche Scientifique ( CNRS ) -Université d'Auvergne - Clermont-Ferrand I ( UdA ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) ( PCVP / CARDIO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ), Université Joseph Fourier - Grenoble 1 (UJF), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Léon Bérard [Lyon]-Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Service d'Endocrinologie (BORDEAUX - Endocrino), Genetique et Biotherapies des Maladies Degeneratives et Proliferatives du Systeme Nerveux (Inserm U745), Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie du Cancer et de l'Infection (BCI ), 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)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie (LIEGE - Endocrino), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pathologie et virologie moléculaire (PVM (UMR_7151)), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université de Reims Champagne-Ardenne (URCA)-Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Service d'Endocrinologie (ANGERS - Endocrino), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Endocrinologie (TOULOUSE - Endocrino), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Institut Gustave Roussy (IGR), Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service d'Endocrinologie (TOURS - Endocrino), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Service d'Endocrinologie (CHRU - Endocrino), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service d'Endocrinologie (NICE - Endocrino), Centre Hospitalier Universitaire de Nice (CHU Nice), Université de Nantes (UN), Centre de Recherche en Cancérologie de Lyon (CRCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Beaujon, Pathologie et virologie moléculaire (PVM), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université de Brest (UBO), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Fédération d'endocrinologie, Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), 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 Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université 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), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Service Endocrinologie, maladies métaboliques et nutrition [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO)
Subjects: Oncology, Male, endocrine system diseases, Proto-Oncogene Proteins c-jun, [SDV]Life Sciences [q-bio], Disease, medicine.disease_cause, MESH: Protein Structure, Tertiary, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, MESH : Female, Genetics (clinical), Mutation, General Medicine, MESH: Follow-Up Studies, MESH : Risk Factors, 3. Good health, 030220 oncology & carcinogenesis, Cohort, MESH : Proto-Oncogene Proteins, Female, MESH : Mutation, MESH : Protein Structure, Tertiary, MESH : Proto-Oncogene Proteins c-jun, MESH : Multiple Endocrine Neoplasia Type 1, Cohort study, medicine.medical_specialty, endocrine system, MESH: Mutation, Genetic counseling, MESH : Male, MESH: Multiple Endocrine Neoplasia Type 1, 030209 endocrinology & metabolism, Biology, 03 medical and health sciences, Internal medicine, Proto-Oncogene Proteins, Genetics, medicine, Multiple Endocrine Neoplasia Type 1, Humans, MEN1, Family, Molecular Biology, MESH: Family, MESH: Humans, MESH: Proto-Oncogene Proteins c-jun, [ SDV ] Life Sciences [q-bio], Proportional hazards model, MESH : Humans, Cancer, MESH : Follow-Up Studies, medicine.disease, MESH: Male, Protein Structure, Tertiary, MESH: Proto-Oncogene Proteins, Cancer research, MESH : Family, MESH: Female, Follow-Up Studies
Abstract: International audience; Multiple endocrine neoplasia syndrome type 1 (MEN1), which is secondary to mutation of the MEN1 gene, is a rare autosomal-dominant disease that predisposes mutation carriers to endocrine tumors. Although genotype-phenotype studies have so far failed to identify any statistical correlations, some families harbor recurrent tumor patterns. The function of MENIN is unclear, but has been described through the discovery of its interacting partners. Mutations in the interacting domains of MENIN functional partners have been shown to directly alter its regulation abilities. We report on a cohort of MEN1 patients from the Groupe d'étude des Tumeurs Endocrines. Patients with a molecular diagnosis and a clinical follow-up, totaling 262 families and 806 patients, were included. Associations between mutation type, location or interacting factors of the MENIN protein and death as well as the occurrence of MEN1-related tumors were tested using a frailty Cox model to adjust for potential heterogeneity across families. Accounting for the heterogeneity across families, the overall risk of death was significantly higher when mutations affected the JunD interacting domain (adjusted HR = 1.88: 95%-CI = 1.15-3.07). Patients had a higher risk of death from cancers of the MEN1 spectrum (HR = 2.34; 95%-CI = 1.23-4.43). This genotype-phenotype correlation study confirmed the lack of direct genotype-phenotype correlations. However, patients with mutations affecting the JunD interacting domain had a higher risk of death secondary to a MEN1 tumor and should thus be considered for surgical indications, genetic counseling and follow-up.
Published: 2013
Full Text: View/download PDF

24. MICA Variant Promotes Allosensitization after Kidney Transplantation

Author: Caroline Poli, Mathias Chatelais, Anne Cesbron-Gautier, Stéphanie Allard, Céline Bressollette, Pierre Tonnerre, Béatrice Charreau, Sylvie Cury, Nathalie Gérard, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), LabEx TRANSPLANTEX [CHU de Nantes], Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Etablissement Français du Sang [Nantes], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Grants from 'L’Agence de Biomédecine' (Recherche et Greffes 2009)., 'La Société de Néphrologie.', 'La région Pays de la Loire' (PROVASC project)., 'La Société Francophone de Transplantation' (SFT)., European Project: LSHBCT-2006-037377, Le Bihan, Sylvie, and European Union–funded Integrated Project in Life Sciences, Genomics and Biotechnology for Health - LSHBCT-2006-037377 - INCOMING
Subjects: Adult, Graft Rejection, Male, Isoantigens, Genotype, Transcription, Genetic, Allosensitization, Primary Cell Culture, Biology, 03 medical and health sciences, 0302 clinical medicine, Antigen, Risk Factors, MHC class I, Humans, Transplantation, Homologous, Genetic Predisposition to Disease, RNA Processing, Post-Transcriptional, RNA, Small Interfering, Aged, 030304 developmental biology, 0303 health sciences, Innate immune system, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Histocompatibility Antigens Class I, Endothelial Cells, Genetic Variation, General Medicine, Middle Aged, NKG2D, Kidney Transplantation, Molecular biology, Immunity, Innate, Tissue Donors, Microvesicles, 3. Good health, Transplantation, stomatognathic diseases, Phenotype, STAT1 Transcription Factor, Basic Research, NK Cell Lectin-Like Receptor Subfamily K, Nephrology, biology.protein, Female, Natural killer cell activation, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; MHC class I-related chain A (MICA) antigens are surface glycoproteins strongly implicated in innate immunity , and the MICA gene is highly polymorphic. Clinical observations suggest a role for donor MICA antigens expressed on transplant endothelial cells in the alloimmune response, but the effect of MICA genotype is not well understood. Here, we investigated the immunologic effect of the A5.1 mutation, related to the common MICA*008 allele. Compared with wild-type endothelial cells (ECs), homozygosity for MICA A5.1 associated with an endothelial phenotype characterized by 7-to 10-fold higher levels of MICA mRNA and MICA proteins at the cell surface, as well as exclusive release in exosomes instead of enzymatic cleavage. Mechanistically, we did not detect quantitative changes in regulatory microRNAs. Functionally, A5.1 ECs enhanced NKG2D interaction and natural killer cell activation, promoting NKG2D-dependent lysis of ECs. In kidney transplant recipients, polyreactive anti-MICA sera bound preferentially to ECs from MICA A5.1 donors, suggesting that MICA*008(A5.1) molecules are the preferential antigenic determinants on ECs of grafts. Furthermore, the incidence of MICA A5.1 mismatch revealed a statistically significant association between donor MICA A5.1 and both anti-MICA sensitization and increased pro-teinuria in kidney recipients. Taken together, these results identify the A5.1 mutation as an immunodo-minant factor and a potential risk factor for transplant survival.
Published: 2013
Full Text: View/download PDF

25. Both the nature of KIR3DL1 alleles and the KIR3DL1/S1 allele combination affect the KIR3DL1 NK-cell repertoire in the French population

Author: Christelle Retière, Julie Esbelin, Nolwenn Legrand, David Senitzer, Céline Bressollette-Bodin, Catherine Willem, Thierry Schneider, Zakia Djaoud, Pauline Rettman, Gaëlle David, Anne Cesbron-Gautier, Katia Gagne, Etablissement Français du Sang [Nantes], Université de Nantes (UN), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), City of Hope Medical Center [Duarte, CA, USA] (HLA laboratory), Hôtel-Dieu de Nantes, and RETIERE, Christelle
Subjects: Receptors, KIR3DS1, [SDV]Life Sciences [q-bio], Immunology, Population, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, White People, 03 medical and health sciences, 0302 clinical medicine, Gene Frequency, Humans, Immunology and Allergy, Allele, Receptor, education, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Allele frequency, Alleles, 030304 developmental biology, Genetics, 0303 health sciences, education.field_of_study, Repertoire, Receptors, KIR3DL1, Phenotype, Null allele, Killer Cells, Natural, [SDV] Life Sciences [q-bio], France, KIR3DL1, 030215 immunology
Abstract: International audience; NK-cell functions are regulated by many activating and inhibitory receptors including KIR3DL1. Extensive allelic polymorphism and variability in expression can directly alter NK-cell phenotype and functions. Here we investigated the KIR3DL1 + NK-cell repertoire, taking into account the allelic KIR3DL1/S1 polymorphism, KIR3DL1 phenotype, and function. All 109 studied individuals possessed at least one KIR3DL1 allele, with weak KIR3DL1*054, or null alleles being frequently present. In KIR3DL1 high/null individuals, we observed a bimodal distribution of KIR3DL1 + NK cells identified by a different KIR3DL1 expression level and cell frequency regardless of a similar amount of both KIR3DL1 transcripts, HLA background, or KIR2D expression. However, this bimodal distribution can be explained by a functional selection following a hierarchy of KIR3DL1 receptors. The higher expression of KIR3DL1 observed on cord blood NK cells suggests the expression of the functional KIR3DL1*004 receptors. Thus, the low amplification of KIR3DL1 high , KIR3DL1*004 NK-cell subsets during development may be due to extensive signaling via these two receptors. Albeit in a nonexclusive manner, individual immunological experience may contribute to shaping the KIR3DL1 NK-cell repertoire. Together, this study provides new insight into the mechanisms regulating the KIR3DL1 NK-cell repertoire.
Published: 2013
Full Text: View/download PDF

26. PIK3R1 Mutations Cause Syndromic Insulin Resistance with Lipoatrophy

Author: Frédéric Huet, Michèle Mathieu-Dramard, Martine Caron-Debarle, Jeanne Amiel, C. Fagour, Christel Thauvin-Robinet, Olivier Lascols, Jacqueline Capeau, Patrick Callier, Marie-Laure Nunes, Damien Picot, Jean-Baptiste Rivière, Bernard Le Luyer, Martine Laville, Judith St-Onge, Delphine Héron, Yves Reznik, Sylvie Odent, Laurence Faivre, Pierre Bitoun, Julien Thevenon, Martine Auclair, Virginie Carmignac, Jean-Michel Petit, Magali Avila, Martine Le Merrer, Laurence Duplomb, Corinne Vigouroux, Department of Experimental Cardiology, Heart Failure Research Center (HFRC)-Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Pathologie de l'Adipocyte et des Cellules Hepatiques, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique des Anomalies du Développement (GAD), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Center of Excellence in Neuroscience, CHU de Montréal, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité Fonctionnelle de Génétique Clinique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Centre de référence 'Déficiences Intellectuelles de Causes Rares' - Paris-Groupe de Recherche Clinique 'Déficience Intellectuelle et Autisme' - Paris, Service de génétique médicale, CHU Amiens-Picardie, Service de Pédiatrie [Jean Verdier], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Jean Verdier [Bondy], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Diabétologie, Institut de Génétique et Développement de Rennes (IGDR), 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 ), Université Joseph Fourier - Grenoble 1 (UJF), Immunovirologie et polymorphisme génétique, Université de Nantes (UN), Laboratoire de cytogénétique (CHU de Dijon), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RH), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), Cancers et préventions, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA)-University of Amsterdam [Amsterdam] (UvA)-Heart Failure Research Center (HFRC), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Centre de Recherche Saint-Antoine (UMRS893), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Endocrinologie, Diabétologie et Maladies Métaboliques (CHU de Dijon), 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 ), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU Tenon [AP-HP], Regional Council of Burgundy, a French government [ANR-10-IAHU], National Heart, Lung, and Blood Institute [HL-102923, HL-102924, HL-102925, HL-102926, HL-103010], ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), Academic Medical Center [Amsterdam] ( AMC ), University of Amsterdam [Amsterdam] ( UvA ) -University of Amsterdam [Amsterdam] ( UvA ) -Heart Failure Research Center (HFRC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université de Montréal-CHU de Montréal, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]-Centre de référence 'Déficiences Intellectuelles de Causes Rares' - Paris-Groupe de Recherche Clinique 'Déficience Intellectuelle et Autisme' - Paris, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris 13 ( UP13 ) -Hôpital Jean Verdier, Institut de Génétique et Développement de Rennes ( IGDR ), 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 ), Université Joseph Fourier - Grenoble 1 ( UJF ), Université de Nantes ( UN ), Centre de Recherche en Nutrition Humaine Rhône-Alpes ( CRNH ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Recherche Agronomique ( INRA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon ( HCL ) -CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] ( UJM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Unité Fonctionnelle de Génétique Clinique [CHU Pitié Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-CHU Saint-Etienne-Hospices Civils de Lyon (HCL)-CHU Grenoble, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13)-Hôpital Jean Verdier [Bondy]
Subjects: Proband, EXPRESSION, medicine.medical_specialty, 030209 endocrinology & metabolism, Biology, medicine.disease_cause, MICE LACKING, Short stature, 03 medical and health sciences, HYPOGLYCEMIA, 0302 clinical medicine, Insulin resistance, PIK3R1, Internal medicine, Report, medicine, Genetics, KINASE, Genetics(clinical), Lipoatrophy, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Mutation, AKT2, [SDV.GEN]Life Sciences [q-bio]/Genetics, RECEPTOR, medicine.disease, 3-KINASE, 3. Good health, Insulin receptor, Endocrinology, AUTOPHOSPHORYLATION, SHORT syndrome, biology.protein, SKELETAL-MUSCLE, GROWTH, medicine.symptom, [ SDV.GEN ] Life Sciences [q-bio]/Genetics
Abstract: International audience; Short stature, hyperextensibility of joints and/or inguinal hernia, ocular depression, Rieger anomaly, and teething delay (SHORT) syndrome is a developmental disorder with an unknown genetic cause and hallmarks that include insulin resistance and lack of subcutaneous fat. We ascertained two unrelated individuals with SHORT syndrome, hypothesized that the observed phenotype was most likely due to de novo mutations in the same gene, and performed whole-exome sequencing in the two probands and their unaffected parents. We then confirmed our initial observations in four other subjects with SHORT syndrome from three families, as well as 14 unrelated subjects presenting with syndromic insulin resistance and/or generalized lipoatrophy associated with dysmorphic features and growth retardation. Overall, we identified in nine affected individuals from eight families de novo or inherited PIK3R1 mutations, including a mutational hotspot (c.1945C>T [p.Arg649Trp]) present in four families. PIK3R1 encodes the p85 alpha, p55 alpha, and p50 alpha regulatory subunits of class IA phosphatidylinositol 3 kinases (PI3Ks), which are known to play a key role in insulin signaling. Functional data from fibroblasts derived from individuals with PIK3R1 mutations showed severe insulin resistance for both proximal and distal PI3K-dependent signaling. Our findings extend the genetic causes of severe insulin-resistance syndromes and provide important information with respect to the function of PIK3R1 in normal development and its role in human diseases, including growth delay, Rieger anomaly and other ocular affections, insulin resistance, diabetes, paucity of fat, and ovarian cysts.
Published: 2013
Full Text: View/download PDF

27. Investigation of the impact of HLA-DPB1 matching status in 10/10 HLA matched unrelated hematopoietic stem cell transplantation: Results of a French single center study

Author: Patricia Herry, Patrice Chevallier, Gilles Folléa, Anne Devys, Mohamad Mohty, Véronique Sébille, Cyrille Touzeau, Katia Gagne, Philippe Moreau, Anne Cesbron Gautier, Centre hospitalier universitaire de Nantes (CHU Nantes), Etablissement Français du Sang [Nantes], Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Université de Nantes (UN), Etablissement Français du Sang [Pays de la Loire] (EFS Pays de la Loire), EFS, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service d'Hématologie Clinique [Nantes], Hôpital Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), and GAGNE, Katia
Subjects: Male, Oncology, medicine.medical_treatment, DNA Mutational Analysis, Graft vs Host Disease, Hematopoietic stem cell transplantation, Single Center, 0302 clinical medicine, Immunology and Allergy, Child, HLA-DP beta-Chains, Histocompatibility Testing, Incidence, Immunogenicity, Hematopoietic Stem Cell Transplantation, General Medicine, Middle Aged, 3. Good health, Treatment Outcome, Child, Preschool, Hematologic Neoplasms, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, Adult, medicine.medical_specialty, Adolescent, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Human leukocyte antigen, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Allele, Permissive, Alleles, Aged, Retrospective Studies, HLA-DPB1, business.industry, Infant, Retrospective cohort study, Survival Analysis, Mutation, business, 030215 immunology
Abstract: International audience; The impact of HLA-DPB1 mismatches after unrelated hematopoietic stem cell transplantation (HSCT) remains controversial. We retrospectively analyzed the impact of permissive/non-permissive HLA-DPB1 mismatches on the outcome of 141 patients who underwent 10/10 HLA allelic-matched unrelated HSCT. Each pair was classified according to the 3 (TCE3) and 4-group (TCE4) algorithm based on DPB1 alleles immunogenicity. Outcome analysis revealed that TCE3 and TCE4 non-permissive HLA-DPB1 disparities were not associated with worsened overall survival, relapse risk neither risk of acute GvHD. Overall, this single center retrospective study does not confirm the adverse prognostic of non-permissive HLA-DPB1 mismatches.
Published: 2012
Full Text: View/download PDF

28. Pretransplant HLA mistyping in diagnostic samples of acute myeloid leukemia patients due to acquired uniparental disomy

Author: BG Hepkema, Jean Villard, Jean-Marie Tiercy, S. Jendly, Anne Cesbron, Jacques Delaunay, M Drouet, S Gimelli, Dominik Heim, André Tichelli, Valérie Dubois, Katia Gagne, F. Sloan-Bena, Etablissement français du sang - Auvergne-Rhône-Alpes (EFS), Geneva University Hospital (HUG), Etablissement Français du Sang [Nantes], University of Groningen [Groningen], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), University Hospital Basel [Basel], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôtel-Dieu de Nantes, CHU Limoges, GAGNE, Katia, and Faculteit Medische Wetenschappen/UMCG
Subjects: Male, Cancer Research, Pathology, Myeloid, Buccal swab, RELAPSE, MISMATCHED HLA, Loss of heterozygosity, 0302 clinical medicine, AML, HLA Antigens, array-comparative genomic hybridization, ddc:616, 0303 health sciences, Comparative Genomic Hybridization, FREQUENT LOSS, Histocompatibility Testing, Myeloid leukemia, Hematology, NORMAL KARYOTYPE, Middle Aged, Uniparental disomy, 3. Good health, Leukemia, Myeloid, Acute, Leukemia, medicine.anatomical_structure, Oncology, HLA typing, 030220 oncology & carcinogenesis, acquired uniparental disomy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Leukemia, Myeloid, Acute/diagnosis/genetics/immunology, Female, HLA Antigens/immunology, EXPRESSION, BLASTS, Adult, Uniparental Disomy/genetics, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, loss of haplotype, Human leukocyte antigen, Biology, Diagnosis, Differential, 03 medical and health sciences, medicine, Humans, 030304 developmental biology, STEM-CELL TRANSPLANTATION, Uniparental Disomy, medicine.disease, luminex microbeads array, Immunology, Comparative genomic hybridization
Abstract: International audience; Although acquired uniparental disomy (aUPD) has been reported in relapse acute myeloid leukemia (AML), pretransplant aUPD involving chromosome 6 is poorly documented. Such events could be of interest because loss of heterozygosity (LOH) resulting from aUPD in leukemic cells may lead to erroneous results if HLA typing for hematopoietic stem cell donor searches is performed on blood samples drawn during blastic crisis. We report here six AML patients whose HLA typing was performed on DNA extracted from peripheral blood obtained at diagnosis. We observed LOH involving the entire HLA region (three patients), HLA-A, B, C (two patients) and HLA-A only (one patient). An array-comparative genomic hybridization showed that copy number was neutral for all loci, thus revealing partial aUPD of chromosome 6p21. When HLA typing was performed on remission blood samples both haplotypes were detected. A 3-4% LOH incidence was estimated in AML patients with high blast counts. Based on DNA mixing experiments, we determined by PCR sequence-specific oligonucleotide hybridization on microbeads arrays a detection threshold for HLA-A, B, DRB1 heterozygosity in blood samples with o80% blasts. Because aUPD may be partial, any homozygous HLA result should be confirmed by a second typing performed on buccal swabs or on blood samples from the patient in remission.
Published: 2012
Full Text: View/download PDF

29. Correlates of adherence to respiratory drugs in COPD patients

Author: Gérard Chatté, F. Denis, Laurent Laforest, Gilles Devouassoux, C. Ritleng, Nathalie Freymond, Christel Saussier, Nadine Passante, Eric Van Ganse, Yves Pacheco, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire d'informatique Fondamentale de Marseille - UMR 6166 (LIF), Université de la Méditerranée - Aix-Marseille 2-Université de Provence - Aix-Marseille 1-Centre National de la Recherche Scientifique (CNRS), Service de Pneumologie, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Pulmonary and Respiratory Medicine, Male, Adult, Pediatrics, medicine.medical_specialty, Chronic Obstructive, Multivariate analysis, Cross-sectional study, MEDLINE, Respiratory System Agents, Severity of Illness Index, Medication Adherence, Pulmonary Disease, Pulmonary Disease, Chronic Obstructive, 03 medical and health sciences, 0302 clinical medicine, Sex Factors, Severity of illness, Medicine, Respiratory drugs, Humans, 030212 general & internal medicine, Respiratory system, Original Research, Aged, COPD, business.industry, Smoking, Public Health, Environmental and Occupational Health, Age Factors, Middle Aged, medicine.disease, 3. Good health, Logistic Models, Cross-Sectional Studies, 030228 respiratory system, Accidental, Multivariate Analysis, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract: International audience; AIMS: To identify the correlates of accidental omissions and intentional interruptions of respiratory therapy in COPD. METHODS: COPD patients (GOLD stages II-IV) were recruited by general practitioners or respiratory physicians. Patients reported in self-report questionnaires their adherence to respiratory drugs (over the past three months) and their perception of therapy. RESULTS: 179 patients were included (mean age 63 years, 24% females). 45% forgot their respiratory therapy, while 30% interrupted it in the absence of any perceived benefit. The risks of accidental omissions were significantly higher when patients complained about having too many medications to take on a daily basis (OR=2.35; 95%CI=1.13-4.89), and among current smokers (OR=2.14; 95%CI=1.07-4.29). Females were more likely to interrupt therapy intentionally (OR=2.40; 95%CI=1.04-5.53). Surprisingly, there was no significant relationship with the number of drugs actually taken by patients. CONCLUSIONS: Adherence to respiratory drugs is inadequate in COPD patients. In order to improve adherence, patients' perception of the burden of therapy should not be overlooked.
Published: 2010
Full Text: View/download PDF

30. Improved KIR gene and HLA-C KIR ligand sequence-specific primer polymerase chain reaction genotyping using whole genome amplification

Author: W. Chainonthee, K. Gagne, G. Böttcher, M. Füssel, Ralf Wassmuth, J.-D. Bignon, Technische Universität Dresden = Dresden University of Technology (TU Dresden), DKMS, Etablissement Français du Sang [Nantes], Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), and GAGNE, Katia
Subjects: Receptors, KIR3DS1, [SDV.IMM] Life Sciences [q-bio]/Immunology, Genotype, KIR Ligand, Immunology, Killer-cell immunoglobulin-like receptor, HLA-C Antigens, Biology, Ligands, Biochemistry, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, law.invention, human leucocyte antigen-C, 03 medical and health sciences, 0302 clinical medicine, Receptors, KIR, law, Genetics, Immunology and Allergy, Humans, Genotyping, Polymerase chain reaction, Polymerase, Alleles, 030304 developmental biology, DNA Primers, Whole Genome Amplification, 0303 health sciences, whole genome amplification, Base Sequence, Multiple displacement amplification, Receptors, KIR3DL1, General Medicine, DNA Probes, HLA, Molecular biology, 3. Good health, genomic DNA, genotyping, killer cell immunoglobulin-like receptor, Receptors, KIR2DL1, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, 030215 immunology, Genome-Wide Association Study
Abstract: International audience; Molecular analysis of genetic polymorphism for clinical or research purposes may be compromised by genomic DNA of limited quality and quantity. In this study, we have successfully tested the feasibility of using whole genome amplification (WGA) to allow genotyping for killer cell immunoglobulin-like receptor (KIR) genes and human leucocyte antigen (HLA)-C KIR ligand dimorphism on HLA-C. WGA was achieved by multiple displacement amplification (MDA) using bacteriophage phi29 polymerase. For KIR genotyping, a revised sequence-specific primer polymerase chain reaction protocol consisting of 23 primer pairs was used avoiding hitherto undetected cross-priming involving KIR2DL1, KIR2DS1, KIR3DL1 and KIR3DS1 alleles. Similarly, MDA-amplified genomic DNA was analyzed for the detection of the HLA-C KIR ligand groups C1 and C2, based on the amino acid K/N dimorphism in position 80.
Published: 2010
Full Text: View/download PDF

31. Control of the HIV infection and drug dosage

Author: Claude H. Moog, Cécile Brunet-François, Marie-José Mhawej, Federico L. Biafore, Institut de Recherche en Communications et en Cybernétique de Nantes (IRCCyN), Mines Nantes (Mines Nantes)-École Centrale de Nantes (ECN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Université de Nantes (UN)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS), Center of Applied Mathematics, School of Science and Technology, National University of San Martin, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Drug, 0209 industrial biotechnology, Mathematical optimization, Parameter identification, Feedback control, media_common.quotation_subject, 0206 medical engineering, Human immunodeficiency virus (HIV), Health Informatics, 02 engineering and technology, medicine.disease_cause, Control inputs, [SPI.AUTO]Engineering Sciences [physics]/Automatic, 020901 industrial engineering & automation, Control theory, Nonlinear systems, Medicine, Pharmacokinetics, Control (linguistics), HIV therapy, media_common, Control algorithm, business.industry, HIV, 020601 biomedical engineering, 3. Good health, Regimen, Pharmacodynamics, Signal Processing, business
Abstract: International audience; An increasing number of sophisticated control algorithms become available in the current literature to optimize the HIV therapy. Unfortunately, the pharmacokinetics and pharmacodynamics of antiretroviral drugs are ignored and these algorithms remain purely theoretic. This issue is investigated explicitly in this paper. An elementary pharmacodynamics model is combined with a non linear feedback control computed from standard engineering methods. It is shown that it results in the design of a realistic dosage regimenwhich drives the immunological system close to the healthy equilibrium state. Although the problem is dealt as a single input system, it is argued that the procedure can be extended to a multitherapy design or to any available control law.
Published: 2010
Full Text: View/download PDF

32. Discrimination between the main activating and inhibitory killer cell immunoglobulin-like receptor positive natural killer cell subsets using newly characterized monoclonal antibodies

Author: Anne Devys, Katia Gagne, Catherine Willem, Jean-Denis Bignon, Gaëlle David, Maelig G. Morvan, Christelle Retière, Gilles Folléa, Nolwenn Kerdudou, Marc Bonneville, Université de Nantes (UN), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Etablissement Français du Sang [Nantes], Laboratoire de génie des procédés - environnement - agroalimentaire (GEPEA), Institut Universitaire de Technologie - Nantes (IUT Nantes), Université de Nantes (UN)-Université de Nantes (UN)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Institut Universitaire de Technologie Saint-Nazaire (IUT Saint-Nazaire), Université de Nantes (UN)-Ecole Polytechnique de l'Université de Nantes (EPUN), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique Bretagne-Pays de la Loire (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Institut Universitaire de Technologie - La Roche-sur-Yon (IUT La Roche-sur-Yon), Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS)-Université Bretagne Loire (UBL)-IMT Atlantique (IMT Atlantique), and RETIERE, Christelle
Subjects: Adult, Genotype, medicine.drug_class, Molecular Sequence Data, Immunology, Killer-cell immunoglobulin-like receptor, chemical and pharmacologic phenomena, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Monoclonal antibody, Natural killer cell, Mice, 03 medical and health sciences, 0302 clinical medicine, Receptors, KIR, Antigen, KIR2DL1, Antibody Specificity, medicine, otorhinolaryngologic diseases, Animals, Humans, Immunology and Allergy, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Mice, Inbred BALB C, 0303 health sciences, Hybridomas, Lymphokine-activated killer cell, Base Sequence, biology, Antibodies, Monoclonal, hemic and immune systems, Original Articles, Natural killer T cell, Lymphocyte Subsets, 3. Good health, Killer Cells, Natural, medicine.anatomical_structure, Receptors, KIR2DL3, Receptors, KIR2DL1, biology.protein, Immunization, Antibody, Sequence Alignment, 030215 immunology
Abstract: International audience; Natural killer (NK) cells are key components of the innate anti-viral and anti-tumour immune responses. NK cell function is regulated by the interaction of killer cell immunoglobulin-like receptors (KIR) with human leucocyte antigen (HLA) class I molecules. In this study, we report on the generation of KIR-specific antibodies allowing for discrimination between activating and inhibitory KIR. For this purpose, BALB/c mice were immunized with human KIR2DS2 recombinant protein. The precise specificity of KIR2DS2-specific clones was determined on KIR-transfected BW cells and KIR-genotyped NK cells. When used in combination with EB6 (KIR2DL1/2DS1) or GL183 (KIR2DL2/2DL3/2DS2), two KIR-specific monoclonal antibodies (mAbs), 8C11 (specific for KIR2DL1/2DL2/2DL3/2DS2) and 1F12 (specific for KIR2DL3/2DS2), discriminated activating KIR2DS1 (8C11(-) EB6(+)) from inhibitory KIR2DL1 (8C11(+) GL183(-)) and KIR2DL2 (1F12(-) GL183(+)), while excluding the main HLA-Cw-specific KIR. Using these mAbs, KIR2DS1 was shown to be expressed on the surface of NK cells from all individuals genotyped as KIR2DS1(+) (n = 23). Moreover, KIR2DS1 and KIR2DL1 were independently expressed on NK cells. We also determined the amino acid position recognized by the 8C11 and 1F12 mAbs, which revealed that some KIR2DL1 allele-encoded proteins are not recognized by 8C11. Because most available anti-KIR mAbs recognize both inhibitory and activating forms of KIR, these newly characterized antibodies should help assess the expression of activating and inhibitory KIR and their functional relevance to NK biology.
Published: 2009
Full Text: View/download PDF

33. P18-01. Exquisite specificity of CTL response to the M184V mutation

Author: Yannick Guilloux, Yves Pacheco, Dorian McIlroy, Virginie Ferré, François Raffi, Clotilde Allavena, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), 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), Anna Laura Ross, and BMC, Ed.
Subjects: lcsh:Immunologic diseases. Allergy, biology, business.industry, Resistance mutation, Bioinformatics, Virology, CTL, Protein structure, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Mutation (genetic algorithm), Poster Presentation, biology.protein, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Antibody, business, lcsh:RC581-607, ComputingMilieux_MISCELLANEOUS
Abstract: International audience; n.a
Published: 2009
Full Text: View/download PDF

34. Cutting Edge: Killer Ig-Like Receptors Mediate 'Missing Self' Recognition In Vivo

Author: Christelle Retière, Jeroen van Bergen, John Trowsdale, Frits Koning, Allan Thompson, Leiden University Medical Center (LUMC), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Etablissement Français du Sang [Nantes], University of Cambridge [UK] (CAM), and RETIERE, Christelle
Subjects: Graft Rejection, Genetically modified mouse, Transgene, Immunology, Mice, Transgenic, Spleen, chemical and pharmacologic phenomena, HLA-C Antigens, Human leukocyte antigen, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Autoantigens, Mice, 03 medical and health sciences, 0302 clinical medicine, In vivo, immune system diseases, medicine, otorhinolaryngologic diseases, Animals, Immunology and Allergy, Receptor, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Mice, Knockout, Antigen Presentation, Stochastic Processes, 0303 health sciences, hemic and immune systems, In vitro, Killer Cells, Natural, Mice, Inbred C57BL, Transplantation, medicine.anatomical_structure, Receptors, KIR2DL2, embryonic structures, Mice, Inbred CBA, NK Cell Lectin-Like Receptor Subfamily A, 030215 immunology
Abstract: Although it is well established that human NK cells are able to detect the absence of autologous HLA class I in vitro by virtue of inhibitory killer Ig-like receptors (KIR), direct evidence that KIR can mediate “missing self” recognition in vivo is lacking. To test this, we generated mice transgenic for a human KIR B-haplotype and HLA-Cw3 on a C57BL/6 background. NK cells in these mice expressed multiple KIR in a stochastic manner, including the HLA-Cw3-specific inhibitory receptor KIR2DL2. KIR and HLA transgenic mice rejected wild-type C57BL/6 spleen cells upon i.v. injection. This rejection was dependent on the presence of the KIR transgene in the host and on the absence of HLA-Cw3 from the injected target cells. Hence, the KIR transgene mediated “missing self” recognition in vivo. We anticipate that this KIR and HLA transgenic mouse will help shed light on KIR and HLA effects in disease and transplantation.
Published: 2009
Full Text: View/download PDF

35. Autologous and allogeneic HLA KIR ligand environments and activating KIR control KIR NK-cell functions

Author: Jean-Denis Bignon, Maelig G. Morvan, Nolwenn Kerdudou, Gilles Folléa, Katia Gagne, Catherine Willem, Christelle Retière, Gaëlle David, Aurore Perrin, Béatrice Clémenceau, Laure Denis, Véronique Sébille, GAGNE, Katia, Etablissement Français du Sang [Nantes], Université de Nantes (UN), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), and 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)
Subjects: Herpesvirus 4, Human, Genotype, [SDV.IMM] Life Sciences [q-bio]/Immunology, KIR Ligand, Immunology, Cell, Autoimmunity, Human leukocyte antigen, NK cells, Biology, Ligands, 03 medical and health sciences, Interleukin 21, 0302 clinical medicine, Receptors, KIR, KIR2DL1, HLA Antigens, medicine, Humans, Immunology and Allergy, Killer cell immunoglobulin-like receptors, Receptor, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Lymphokine-activated killer cell, Cell Differentiation, NK repertoire, Molecular biology, Killer Cells, Natural, medicine.anatomical_structure, HLA class I molecules, Interleukin 12, [SDV.IMM]Life Sciences [q-bio]/Immunology, Protein Binding, 030215 immunology
Abstract: International audience; NK-cell function is regulated by a balance between inhibitory and activating killer cell immunoglobulin-like receptors (KIR) that specifically recognize HLA class I molecules. Using KIR-specific mAb to discriminate between KIR2DS1 and KIR2DL1 receptors, we show that KIR2DS1 + NK cells are C2-alloreactive only from C2 À individuals. Moreover, using an in vitro model of NK-cell expansion, we show here that the frequency of KIR2DL1 + NK cells is significantly higher in the absence of C2 ligand on stimulator EBV-B cells than in its presence. This observation was made regardless of the presence or absence of the autologous C2 ligand, suggesting that the C2 À EBV-B stimulator cells used in this in vitro model could activate unlicensed KIR2DL1 + NK cells. In the case of KIR2DL1 + /S1 + genotyped individuals, KIR2DS1 + NK-cell frequency was increased after stimulation with C2 + compared with C2 À stimulator B cells, but only from C2 À individuals. Altogether, these data highlight the C2 alloreactivity of KIR2DS1 + NK cells that is only observed in C2 À individuals. These results provide new insights into the way in which NK KIR cell expansion might be regulated in an allogeneic environment.
Published: 2008
Full Text: View/download PDF

36. Projet d'éducation du patient asthmatique et proposition d'une méthode d'évaluation

Author: Van Ganse, Eric, Laforest, L., Devouassoux, Gilles, Freymond, Nathalie, Arkhis, Ahmed, BOUVERET, Laetitia, BIESSY, Claire, REICHER, Jaqueline, Ecochard, René, Pacheco, Yves, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, laboratoire du sommeil, CHU Grenoble, Service des maladies respiratoires, Hospices Civils de Lyon (HCL), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), École normale supérieure - Lyon (ENS Lyon), Service de Biostatistiques [Lyon], Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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 Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-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), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), and École normale supérieure de Lyon (ENS de Lyon)
Subjects: Pédagogie, Méthodologie, Prévention, Recrutement, Méthode, Asthme, Homme, Appareil respiratoire [pathologie], Méthode pédagogique, Bronchopneumopathie obstructive, Soins autogérés, Malade, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Evaluation enseignement, Enseignement, Evaluation
Abstract: International audience; Contexte et objectifs : L'asthme est un enjeu majeur de santé publique en raison de la mortalité, de la morbidité, des dépenses de soins engendrées et des conséquences sur la qualité de vie des patients. Un programme éducatif a été mis en place pour apporter aux patients asthmatiques une formation complémentaire à celle reçue chez le médecin généraliste. Méthodes : Quatre séances trimestrielles sont prévues. La formation commence par un bilan initial comprenant un examen médical approfondi et un recueil d'informations (contrôle de l'asthme, qualité de vie, connaissances sur la maladie et satisfaction vis-à-vis des traitements). Au cours de ces séances, les patients voient un médecin, un kinésithérapeute et un psychologue. Ils reçoivent des informations détaillées sur la physiopathologie de l'asthme et les traitements reçus. Ils apprennent à utiliser des plans d'action en cas de crise et à tenir un carnet de bord. Un bilan final identique au bilan initial est prévu au terme de l'étude, 12 mois plus tard. Cent cinquante patients sont randomisés dans deux groupes : "éducation immédiate" (n=75) et "éducation différée" contrôle (n=75). Le groupe éducation immédiate bénéficie des quatre séances éducatives tandis que le groupe "éducation différée" n'a que la première séance. La survenue d'exacerbations de l'asthme pendant le suivi sera comparée entre les deux groupes, tout comme les évolutions respectives entre le bilan initial et le bilan final du contrôle de l'asthme, de la qualité de vie, de la satisfaction vis-à-vis des traitements, et du niveau de connaissance du patient. Les difficultés méthodologiques pour la mise en place et l'évaluation du projet éducatif sont évoquées dans l'article. Résultats préliminaires et discussion : A ce jour, dix patients ont été inclus dans le programme éducatif, qui a été bien accueilli par les patients. Certaines difficultés de recrutement sont analysées ; elles devront faire l'objet de mesures spécifiques.
Published: 2007

37. Influence of sociodemographic factors on quality of life during pollen season in seasonal allergic rhinitis patients

Author: Michel Aubier, Eric Van Ganse, Françoise Neukirch, Gilles Devouassoux, G Pietri, Jean Bousquet, Laurent Laforest, Yves Pacheco, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre de Recherche en Biologie Forestière, Pavillon Charles-Eugène-Marchand, Université Laval [Québec] (ULaval), Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pneumologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), laboratoire du sommeil, CHU Grenoble, Service des maladies respiratoires, Hospices Civils de Lyon (HCL), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), and Université de Nantes (UN)-Université de Nantes (UN)
Subjects: Pulmonary and Respiratory Medicine, Ragweed, Male, Adult, Questionnaires, Rural Population, medicine.medical_specialty, Allergy, Multivariate analysis, Adolescent, Immunology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Allergic, Sex Factors, Quality of life, Surveys and Questionnaires, medicine, Immunology and Allergy, Humans, 030212 general & internal medicine, Prospective cohort study, Asthma, Demography, Rhinitis, Seasonal, biology, business.industry, Rhinitis, Allergic, Seasonal, Middle Aged, Allergens, medicine.disease, biology.organism_classification, humanities, Surgery, 030228 respiratory system, Quality of Life, Pollen, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, Seasons, Rural area, business, Cohort study
Abstract: International audience; BACKGROUND: Quality of life (QOL) is an important outcome in asthma and seasonal allergic rhinitis (SAR), and its determinants are imperfectly understood. More specifically, the influence of sociodemographic factors on QOL in patients with SAR has been so far little investigated. OBJECTIVE: To examine the changes of QOL during the pollen season in patients with isolated SAR or SAR associated with asthma. METHODS: A prospective cohort study was conducted in southern France. Outpatients aged 18 to 60 years and regularly treated by respiratory physicians for SAR (with or without associated asthma) were identified. Patients were recruited before the grass or ragweed pollination period. At peak pollination, patients completed the French versions of the Mini Rhino-conjunctivitis Quality of Life Questionnaire (mini-RQLQ) and the 12-item Short-Form Health Survey (SF-12) physical component summary (PCS) and mental component summary (MCS). RESULTS: A total of 135 patients was included, 83 with isolated SAR and 52 with associated asthma (mean age, 35.4 years; SD, 10.6 years; 56% female). At pollen peak, QOL scores were lower in women for all instruments, with significant effects on SF-12 MCS and PCS scores in multivariate analyses. Likewise, a university-level education was an independent predictor of higher SF-12 PCS and MCS scores. Patients who lived in rural areas had significantly poorer QOL at pollen peak, as measured by the mini-RQLQ (P = .002) and SF-12 PCS (P = .008). No influence of age, presence of an animal at home, or smoking status could be identified on any QOL scores. CONCLUSIONS: Being a woman, living in the countryside, and having a lower education level were all independent predictors of poorer QOL of SAR patients. These factors must be taken into account when interpreting QOL of patients with SAR. Further studies are needed to confirm these results.
Published: 2005
Full Text: View/download PDF

38. Association between asthma control in children and loss of workdays by caregivers

Author: Eric Van Ganse, Donald Yin, Neville Dickson, Vasilisa Sazonov Kocevar, Laurent Laforest, Frédéric Gormand, Yves Pacheco, Health Service and Performance Research (HESPER), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), and Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
Subjects: Pulmonary and Respiratory Medicine, Male, Questionnaires, medicine.medical_specialty, Activities of daily living, Adolescent, Cross-sectional study, Immunology, Status Asthmaticus, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Patient Education as Topic, immune system diseases, Surveys and Questionnaires, 030225 pediatrics, Severity of illness, Absenteeism, Activities of Daily Living, medicine, Immunology and Allergy, Humans, Anti-Asthmatic Agents, Child, Asthma, Retrospective Studies, business.industry, Public health, Retrospective cohort study, Odds ratio, medicine.disease, Drug Utilization, 3. Good health, respiratory tract diseases, Treatment Outcome, Cross-Sectional Studies, 030228 respiratory system, Caregivers, Family medicine, Physical therapy, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, Follow-Up Studies
Abstract: International audience; BACKGROUND: Although the economic burden of pediatric asthma is a significant public health issue, the loss of workdays by caregivers because of their children's asthma remains scarcely investigated. OBJECTIVES: To evaluate asthma-related loss of workdays incurred by caregivers of asthmatic children and its association with the level of asthma control. METHODS: A retrospective observational study was conducted based on a French computerized general practitioners' database and a survey questionnaire. Children aged 6 to 16 years with persistent asthma (Global Initiative for Asthma grade \\textgreater or = 2) were included in the study. Level of children's asthma control was evaluated from recent asthma symptoms. Caregivers reported the number of workdays lost because of their child's asthma during the 12-month study. RESULTS: Nearly 30% of caregivers lost workdays during the study because of their children's asthma. More than 13% of caregivers lost more than 5 days. Caregiver absenteeism significantly correlated with all components of asthma control (use of relievers, nocturnal symptoms, impairment of activities, and asthma crises). A significant 8-fold risk of losing more than 5 workdays by caregivers was observed when the child's asthma was poorly controlled (odds ratio, 8.6; 95% confidence interval, 2.4-30.5); caregivers' absenteeism also increased significantly with the number of episodes of oral corticosteroid use during the study. CONCLUSIONS: Caregivers' loss of workdays owing to their children's asthma is substantial and is highly correlated with the level of asthma control. These findings highlight the necessity of educational programs for children with poor asthma control and their caregivers to prevent severe asthma attacks that lead to caregiver absenteeism.
Published: 2004

39. Caractérisation des interactions entre les cellules dendritiques myéloïdes humaines et le BKPyV

Author: Franck Halary, Dorian McIlroy, Mathieu Sikorski, Céline Bressollette-Bodin, Antoine Touzé, TL Tang, Institut National de la Santé et de la Recherche Médicale (INSERM), Immunovirologie et polymorphisme génétique, Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, and Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)
Subjects: 03 medical and health sciences, Medical Laboratory Technology, 0302 clinical medicine, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Biochemistry (medical), 030204 cardiovascular system & hematology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 3. Good health, Analytical Chemistry
Abstract: National audience; Le polyomavirus BK (ou BKPyV) est un virus ubiquitaire infectant de manière asymptomatique 80 % de la population pendant l’enfance. Suite à la primo-infection, il entre en phase de réplication à bas bruit dans les epithelia réno-urinaires. Suite à une transplantation, la prise d’un traitement immunosuppresseur diminue les réponses immunitaires et donc le contrôle des infections virales notamment. Dans ce contexte, le BKPyV se comporte en pathogène opportuniste et se réplique activement dans le rein. Cette infection active peut en outre induire le développement d’une néphropathie évolutive, la néphropathie associée aux polyomavirus ou PVAN, caractérisée par une virémie et pouvant conduire au rejet du greffon. La gravité de cette atteinte rénale a été corrélée à l’établissement de cette virémie, dont la cause reste mal connue. Ainsi, le BKPyV est reconnu comme une cause infectieuse majeure de rejet de greffe. Basé sur des propriétés des cellules dendritiques (DC) aujourd’hui bien décrites, telles que la capacité à protéger des virus en surface et à les transmettre à d’autres cellules, et l’observation de DC à proximité immédiate des sites de réactivation du virus dans le rein normal, notre hypothèse est que les DC sont capables de capter le BKPyV et de le transporter avec elles dans l’organisme, favorisant l’établissement de la virémie. Notre groupe a ainsi pu démontrer par cytométrie de flux et par imagerie confocale, que des particules virales infectieuses, mais également des pseudo-particules (VLP), peuvent être capturées spécifiquement par des cellules dendritiques myéloïdes (mDC) in vitro. En outre, nous avons également démontré que la protéine VP1, composant majeur de la capside, était incapable d’activer les mDC. Enfin, nous avons montré que le virus capturé par les mDC peut être transmis à des cellules épithéliales tubulaires rénales très susceptibles à l’infection BKPyV. En conclusion, nous pouvons dire que cette interaction entre des particules infectieuses de BKPyV avec notre modèle de mDC est décrite pour la première fois. Elle doit être confirmée dans d’autres modèles et approfondie. Nous envisageons en collaboration avec les néphrologues nantais d’investiguer le rôle de ces cellules dans les greffons de reins humains après transplantation.
Published: 2014
Full Text: View/download PDF

40. Impact of Graft-Versus-Graft Natural Killer Cell Alloreactivity on Single Unit Dominance After Double Umbilical Cord Blood Transplantation.

Author: Rettman P, Willem C, Volteau C, Legrand N, Chevallier P, Lodé L, Esbelin J, Cesbron A, Bonneville M, Moreau P, Senitzer D, Retière C, and Gagne K
Subjects: Apoptosis, Cells, Cultured, Cytotoxicity, Immunologic, France, Genotype, Graft vs Host Disease pathology, HLA Antigens genetics, Humans, Killer Cells, Natural pathology, Phenotype, Receptors, KIR3DL1 genetics, Retrospective Studies, Treatment Outcome, Cord Blood Stem Cell Transplantation adverse effects, Graft vs Host Disease immunology, HLA Antigens immunology, Histocompatibility, Killer Cells, Natural immunology, Lymphocyte Activation, Receptors, KIR3DL1 immunology
Abstract: Background: Natural killer (NK) cell alloreactivity is favored after double umbilical cord blood transplantation (dUCBT) in which cord blood (UCB) units and patients are often HLA class I mismatched. Generally, only 1 UCB unit persists after dUCBT. We hypothesize, that NK cell alloreactivity mediated by killer cell immunoglobulin-like receptor (KIR)-HLA interactions may explain the dominance of 1UCB unit over the other after dUCBT., Methods: We investigated the impact of KIR NK cell alloreactivities on the dominance of 1 full UCB unit in 50 dUCBT. We analyzed the effects of the KIR/HLA genetic incompatibilities and studied cord blood cells at both the phenotypic and functional levels., Results: The genetic combination of KIR3DL1 loser UCB unit/Bw4 winner UCB unit determined both the dominance of 1 UCB unit (hazards ratio, 2.88 [1.32-6.27], P = 0.0077) and correlated with an increased incidence of relapse (hazards ratio, 4.91 [1.39-17.3], P = 0.0134). It is interesting to note that cord blood cells exhibited extremely low HLA class I expression. Moreover, resting cord blood KIR3DL1 NK cells exhibited a basal alloreactivity against Bw4 target cells that increased upon activation, thus triggering death by apoptosis., Conclusions: Our unicentric study suggests, for the first time, the significant impact of KIR NK cell alloreactivity in the determination of which UCB unit will dominate in dUCBT.
Published: 2017
Full Text: View/download PDF

41. Decrease of blood anti-α1,3 Galactose Abs levels in multiple sclerosis (MS) and clinically isolated syndrome (CIS) patients.

Author: Le Berre L, Rousse J, Gourraud PA, Imbert-Marcille BM, Salama A, Evanno G, Semana G, Nicot A, Dugast E, Guérif P, Adjaoud C, Freour T, Brouard S, Agbalika F, Marignier R, Brassat D, Laplaud DA, Drouet E, Van Pesch V, and Soulillou JP
Subjects: Adolescent, Adult, Aged, Child, Child, Preschool, Epstein-Barr Virus Infections blood, Epstein-Barr Virus Infections immunology, Female, Humans, Male, Middle Aged, Pregnancy, Young Adult, Demyelinating Diseases blood, Demyelinating Diseases immunology, Galactose immunology, Immunoglobulin G blood
Abstract: The etiology of multiple sclerosis (MS) remains elusive. Among the possible causes, the increase of anti-Neu5Gc antibodies during EBV primo-infection of Infectious mononucleosis (IMN) may damage the integrity of the blood-brain barrier facilitating the transfer of EBV-infected B cells and anti-EBV T cell clones in the brain. We investigated the change in titers of anti-Neu5Gc and anti-α1,3 Galactose antibodies in 49 IMN, in 76 MS, and 73 clinically isolated syndrome (CIS) patients, as well as age/gender-matched healthy individuals. Anti-Gal and anti-Neu5Gc are significantly increased during IMN (p=0.02 and p<1.10 -4 respectively), but not in acute CMV primo-infection. We show that, whereas there was no change in anti-Neu5Gc in MS/CIS, the two populations exhibit a significant decrease in anti-Gal (combined p=2.7.10 -3 ), in contrast with patients with non-MS/CIS central nervous system pathologies. Since anti-Gal result from an immunization against α1,3 Gal, lacking in humans but produced in the gut, our data suggest that CIS and MS patients have an altered microbiota or an altered response to this microbiotic epitope., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2017
Full Text: View/download PDF

42. Role of IL-12 in overcoming the low responsiveness of NK cells to missing self after traumatic brain injury.

Author: Roquilly A, David G, Cinotti R, Vourc'h M, Morin H, Rozec B, Retière C, and Asehnoune K
Subjects: Adult, Aged, Aged, 80 and over, Cell Degranulation immunology, Female, Genes, MHC Class I, Genes, MHC Class II, Humans, Interferon-gamma immunology, Male, Middle Aged, Young Adult, Brain Injuries, Traumatic immunology, Interleukin-12 immunology, Killer Cells, Natural immunology
Abstract: Blood samples from 32 patients with severe Traumatic brain injury (TBI) were studied and compared with 11 cardiac surgery patients, and 29 healthy controls. A dramatic decreased expression of HLA class I molecules on monocytes was associated with increased KIR+ NK cell frequency in TBI patients. Overall, the phenotype of TBI NK cells marked by KIR and CD57 expression and lower level of NKp46 and DNAM-1 reflected a differentiated state. The NK-cell response to missing self was marked by lower degranulation and lower IFN-γ production after stimulation with HLA class I deficient cell line. In contrast, the NK-cell ADCC was not altered. IL-12 was able to restore both IFN-γ production and the cytotoxicity capacities of NK cells. This study provides the first extensive description of the phenotype and functions of NK cells in TBI patients. Further evaluation of IL-12 treatment to overcome immunosuppression-induced nosocomial infections is warranted., (Copyright © 2015 Elsevier Inc. All rights reserved.)
Published: 2017
Full Text: View/download PDF

43. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD.

Author: Carapito R, Jung N, Kwemou M, Untrau M, Michel S, Pichot A, Giacometti G, Macquin C, Ilias W, Morlon A, Kotova I, Apostolova P, Schmitt-Graeff A, Cesbron A, Gagne K, Oudshoorn M, van der Holt B, Labalette M, Spierings E, Picard C, Loiseau P, Tamouza R, Toubert A, Parissiadis A, Dubois V, Lafarge X, Maumy-Bertrand M, Bertrand F, Vago L, Ciceri F, Paillard C, Querol S, Sierra J, Fleischhauer K, Nagler A, Labopin M, Inoko H, von dem Borne PA, Kuball J, Ota M, Katsuyama Y, Michallet M, Lioure B, Peffault de Latour R, Blaise D, Cornelissen JJ, Yakoub-Agha I, Claas F, Moreau P, Milpied N, Charron D, Mohty M, Zeiser R, Socié G, and Bahram S
Subjects: Acute Disease, Adolescent, Adult, Aged, Allografts, Child, Child, Preschool, Chronic Disease, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, NK Cell Lectin-Like Receptor Subfamily K genetics, Retrospective Studies, Graft vs Host Disease epidemiology, Graft vs Host Disease etiology, Graft vs Host Disease genetics, Graft vs Host Disease prevention & control, HLA Antigens genetics, Hematopoietic Stem Cell Transplantation, Histocompatibility Antigens Class I genetics, Histocompatibility Testing, Linkage Disequilibrium
Abstract: Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice., (© 2016 by The American Society of Hematology.)
Published: 2016
Full Text: View/download PDF

44. New insights on the natural killer cell repertoire from a thorough analysis of cord blood cells.

Author: Rettman P, Willem C, David G, Riou R, Legrand N, Esbelin J, Cesbron A, Senitzer D, Gagne K, and Retière C
Subjects: Adult, Cells, Cultured, Fetal Blood metabolism, Humans, Killer Cells, Natural metabolism, Lymphocyte Activation, Fetal Blood immunology, Histocompatibility Antigens Class I metabolism, Killer Cells, Natural immunology, Receptors, KIR metabolism, Receptors, Natural Killer Cell metabolism
Abstract: Although CB NK cells are characterized as immature lymphocytes, their impressive expansion and efficient graft-versus-leukemia response have been highlighted early after UCBT. To better evaluate their potential as source of effective NK cells, we revisited the study of NK cell repertoire from a large cohort of CB samples. Our study showed that the CB NK cell repertoire appears to be constructed early, depending on KIR gene content, but not on the autologous HLA environment. NKG2A was expressed on a large proportion of CB NK cells that inversely correlated with KIR(+) NK cell frequency. Self-HLA class I molecule-educated CB KIR(+) NK cells present a lower spontaneous lysis than do their adult counterparts, which is probably related to the low expression of activating NK receptors. We describe for the first time a proliferative and cytotoxic NKG2C(+) NK cell subset representing more than 10% of CB NK cells. NKG2A strongly inhibited CB NK cell degranulation, and its coexpression on NKG2C(+) NK cells may contribute to limiting their activation. Overall, the CB NK cell repertoire is constructed early and harbors numerous functional abilities shared by adult NK cells. In addition, their naïve viral status and fast expansion confer numerous advantages in immunotherapy on CB NK cells., (© Society for Leukocyte Biology.)
Published: 2016
Full Text: View/download PDF

45. Human Cytomegalovirus Infection Enhances NK Cell Activity In Vitro.

Author: Tschan-Plessl A, Stern M, Schmied L, Retière C, Hirsch HH, Garzoni C, van Delden C, Boggian K, Mueller NJ, Berger C, Villard J, Manuel O, Meylan P, and Terszowski G
Abstract: Background: Occurring frequently after solid organ and hematopoietic stem cell transplantation, cytomegalovirus (CMV) replication remains a relevant cause of mortality and morbidity in affected patients. Despite these adverse effects, an increased alloreactivity of natural killer (NK) cells after CMV infection has been assumed, but the underlying physiopathological mechanisms have remained elusive., Methods: We used serial analyses of NK cells before and after CMV infection in kidney transplant recipients as an in vivo model for CMV primary infection to explore the imprint of CMV infection using every patient as their own control: We analyzed NK cell phenotype and function in 47 CMV seronegative recipients of CMV seropositive kidney grafts, who developed CMV primary infection posttransplant. Seronegative recipients of seronegative kidney grafts served as controls., Results: We observed a significant increase of NKG2C expressing NK cells after CMV infection (mean increase, 17.5%; 95% confidence interval [95% CI], 10.2-24.9, P < 0.001), whereas cluster of differentiation (CD)57 expressing cells decreased (mean decrease, 14.1%; 95% CI, 8.0-20.2; P < 0.001). Analysis of killer immunoglobulin-like receptor (KIR) expression showed an increase of cells expressing KIR2DL1 as their only inhibitory KIR in patients carrying the cognate ligand HLA-C2 (mean increase, 10.0%; 95% CI, 1.7-18.3; P = 0.018). In C2-negative individuals, KIR2DL1 expression decreased (mean decrease, 3.9%; 95% CI, 1.6-6.2; P = 0.001). As for activating KIR, there was no conclusive change pattern. Most importantly, we observed a significantly higher NK cell degranulation and IFNγ production in response to different target cells (target K562, CD107a: mean increase, 9.9%; 95% CI, 4.8-15.0; P < 0.001; IFNγ: mean increase, 6.6%; 95% CI, 1.6-11.1; P < 0.001; target MRC-5, CD107a: mean increase, 6.9%; 95% CI, 0.7-13.1; P = 0.03; IFNγ: mean increase, 4.8%; 95% CI, 1.7-7.8; P = 0.002)., Conclusions: We report evidence for an increased function of NK cells induced by CMV infection. This increased in vitro functionality was seen in NKG2C-positive and NKG2C-negative subsets, arguing for an NKG2C independent mechanism of action., Competing Interests: The authors declare no conflicts of interest.
Published: 2016
Full Text: View/download PDF

46. Use of killer cell immunoglobulin-like receptor genes as early markers of hematopoietic chimerism after double-umbilical cord blood transplantation.

Author: Rettman P, Legrand N, Willem C, Lodé L, Chevallier P, Cesbron A, Senitzer D, Retière C, and Gagne K
Subjects: Biomarkers blood, Female, Humans, Male, Cord Blood Stem Cell Transplantation, Polymorphism, Single Nucleotide, Receptors, KIR blood, Receptors, KIR genetics, Recovery of Function, Transplantation Chimera blood, Transplantation Chimera genetics
Published: 2015
Full Text: View/download PDF

47. BK polyomavirus: virus-cell interactions, host immune response, and viral pathogenesis.

Author: Mazalrey S, Mc Ilroy D, and Bressollette-Bodin C
Abstract: The BK polyomavirus (BKPyV) is one of the main human polyomaviruses. After primary infection, it establishes a persistent infection, and acts as an opportunistic pathogen, innocuous in immunocompetent hosts, but causing potentially serious pathology in the context of immunosuppression, in particular in kidney and hematopoietic stem cell graft recipients. Much progress has been made in recent years in the description of virus-cell interactions, but many aspects of viral physiopathology remain mysterious, principally due to the asymptomatic nature of infection in immunocompetent individuals and the lack of an animal model. The characteristics of the antiviral immune response are beginning to become more clearly understood, particularly in kidney transplant patients. Work in these areas is important in order to identify patients at high risk of developing a severe infection. Indeed, in the absence of an effective antiviral therapy few therapeutic options are available, and patient management remains based on modulation of immunosuppressive therapy.
Published: 2015
Full Text: View/download PDF

48. Hydrocortisone prevents immunosuppression by interleukin-10+ natural killer cells after trauma-hemorrhage.

Author: Roquilly A, Broquet A, Jacqueline C, Masson D, Segain JP, Braudeau C, Vourc'h M, Caillon J, Altare F, Josien R, Retière C, Villadangos J, and Asehnoune K
Subjects: Adolescent, Adult, Aged, Animals, Cross Infection prevention & control, Cytokines immunology, Dendritic Cells immunology, Dose-Response Relationship, Drug, Female, Humans, Male, Mice, Middle Aged, Pneumonia, Bacterial prevention & control, Staphylococcal Infections prevention & control, Trauma Severity Indices, Young Adult, Anti-Inflammatory Agents pharmacology, Hydrocortisone pharmacology, Interleukin-10 immunology, Killer Cells, Natural immunology, Wounds and Injuries physiopathology
Abstract: Objective: Trauma induces a state of immunosuppression, which is responsible for the development of nosocomial infections. Hydrocortisone reduces the rate of pneumonia in patients with trauma. Because alterations of dendritic cells and natural killer cells play a central role in trauma-induced immunosuppression, we investigated whether hydrocortisone modulates the dendritic cell/natural killer cell cross talk in the context of posttraumatic pneumonia., Design: Experimental study., Settings: Research laboratory from an university hospital., Subjects: Bagg Albino/cJ mice (weight, 20-24 g)., Interventions: First, in an a priori substudy of a multicenter, randomized, double-blind, placebo-controlled trial of hydrocortisone (200 mg/d for 7 d) in patients with severe trauma, we have measured the blood levels of five cytokines (tumor necrosis factor-α, interleukin-6, interleukin-10, interleukin-12, interleukin-17) at day 1 and day 8. In a second step, the effects of hydrocortisone on dendritic cell/natural killer cell cross talk were studied in a mouse model of posttraumatic pneumonia. Hydrocortisone (0.6 mg/mice i.p.) was administered immediately after hemorrhage. Twenty-four hours later, the mice were challenged with Staphylococcus aureus (7 × 10 colony-forming units)., Measurements and Main Results: Using sera collected during a multicenter study in patients with trauma, we found that hydrocortisone decreased the blood level of interleukin-10, a cytokine centrally involved in the regulation of dendritic cell/natural killer cell cluster. In a mouse model of trauma-hemorrhage-induced immunosuppression, splenic natural killer cells induced an interleukin-10-dependent elimination of splenic dendritic cell. Hydrocortisone treatment reduced this suppressive function of natural killer cells and increased survival of mice with posthemorrhage pneumonia. The reduction of the interleukin-10 level in natural killer cells by hydrocortisone was partially dependent on the up-regulation of glucocorticoid-induced tumor necrosis factor receptor-ligand (TNFsf18) on dendritic cell., Conclusions: These data demonstrate that trauma-induced immunosuppression is characterized by an interleukin-10-dependent elimination of dendritic cell by natural killer cells and that hydrocortisone improves outcome by limiting this immunosuppressive feedback loop.
Published: 2014
Full Text: View/download PDF

49. Mathematical Modeling of HIV Dynamics After Antiretroviral Therapy Initiation: A Review.

Author: Rivadeneira PS, Moog CH, Stan GB, Brunet C, Raffi F, Ferré V, Costanza V, Mhawej MJ, Biafore F, Ouattara DA, Ernst D, Fonteneau R, and Xia X
Abstract: This review shows the potential ground-breaking impact that mathematical tools may have in the analysis and the understanding of the HIV dynamics. In the first part, early diagnosis of immunological failure is inferred from the estimation of certain parameters of a mathematical model of the HIV infection dynamics. This method is supported by clinical research results from an original clinical trial: data just after 1 month following therapy initiation are used to carry out the model identification. The diagnosis is shown to be consistent with results from monitoring of the patients after 6 months. In the second part of this review, prospective research results are given for the design of individual anti-HIV treatments optimizing the recovery of the immune system and minimizing side effects. In this respect, two methods are discussed. The first one combines HIV population dynamics with pharmacokinetics and pharmacodynamics models to generate drug treatments using impulsive control systems. The second one is based on optimal control theory and uses a recently published differential equation to model the side effects produced by highly active antiretroviral therapy therapies. The main advantage of these revisited methods is that the drug treatment is computed directly in amounts of drugs, which is easier to interpret by physicians and patients.
Published: 2014
Full Text: View/download PDF

50. Large spectrum of HLA-C recognition by killer Ig-like receptor (KIR)2DL2 and KIR2DL3 and restricted C1 SPECIFICITY of KIR2DS2: dominant impact of KIR2DL2/KIR2DS2 on KIR2D NK cell repertoire formation.

Author: David G, Djaoud Z, Willem C, Legrand N, Rettman P, Gagne K, Cesbron A, and Retière C
Subjects: Alleles, Cells, Cultured, Genotype, HLA-C Antigens genetics, HLA-C Antigens metabolism, Humans, Lymphocyte Activation genetics, Lymphocyte Activation immunology, Receptors, KIR2DL1 immunology, Receptors, KIR2DL2 immunology, Receptors, KIR2DL3 immunology, HLA-C Antigens immunology, Killer Cells, Natural immunology, Receptors, KIR immunology
Abstract: The interactions of killer Ig-like receptor 2D (KIR2D) with HLA-C ligands contribute to functional NK cell education and regulate NK cell functions. Although simple alloreactive rules have been established for inhibitory KIR2DL, those governing activating KIR2DS function are still undefined, and those governing the formation of the KIR2D repertoire are still debated. In this study, we investigated the specificity of KIR2DL1/2/3 and KIR2DS1/2, dissected each KIR2D function, and assessed the impact of revisited specificities on the KIR2D NK cell repertoire formation from a large cohort of 159 KIR and HLA genotyped individuals. We report that KIR2DL2(+) and KIR2DL3(+) NK cells reacted similarly against HLA-C(+) target cells, irrespective of C1 or C2 allele expression. In contrast, KIR2DL1(+) NK cells specifically reacted against C2 alleles, suggesting a larger spectrum of HLA-C recognition by KIR2DL2 and KIR2DL3 than KIR2DL1. KIR2DS2(+) KIR2DL2(-) NK cell clones were C1-reactive irrespective of their HLA-C environment. However, when KIR2DS2 and KIR2DL2 were coexpressed, NK cell inhibition via KIR2DL2 overrode NK cell activation via KIR2DS2. In contrast, KIR2DL1 and KIR2DS2 had an additive enhancing effect on NK cell responses against C1C1 target cells. KIR2DL2/3/S2 NK cells predominated within the KIR repertoire in KIR2DL2/S2(+) individuals. In contrast, the KIR2DL1/S1 NK cell compartment is dominant in C2C2 KIR2DL2/S2(-) individuals. Moreover, our results suggest that together with KIR2DL2, activating KIR2DS1 and KIR2DS2 expression limits KIR2DL1 acquisition on NK cells. Altogether, our results suggest that the NK cell repertoire is remolded by the activating and inhibitory KIR2D and their cognate ligands.
Published: 2013
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

59 results on '"Immunovirologie et polymorphisme génétique"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources