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1. Molecular and functional signatures of distinct subpopulations of extracellular vesicles provide a rationale for beta-cell mediated immune disease

Author

MIGNOT, Grégoire, Giri, Khem Raj, De Beaurepaire, Laurence, Jegou, Dominique, Lavy, Margot, Mosser, Mathilde, Dupont, Aurelien, Fleurisson, Romain, Dubreil, Laurence, Pichon, Julien, van Endert, Peter Van, Bach, Jean-Marie, Bosch, Steffi, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Microscopie de Rennes (MRic), Université de Rennes (UR)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Physiopathologie Animale et bioThérapie du muscle et du système nerveux (PAnTher), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Expertise en Anatomie Pathologique (APEX), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris Descartes - Paris 5 (UPD5), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021

2. Can We Extrapolate From a Cmah -/- Ldlr -/- Mouse Model a Susceptibility for Atherosclerosis in Humans?

Author

Soulillou, Jean-Paul, Cozzi, Emanuele, Galli, Cesare, Bach, Jean-Marie, 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), University Hospital of Padua, Avantea Laboratory of Reproductive Technologies [Cremona, Italy], Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Le Bihan, Sylvie, Azienda Ospedale Università di Padova = Hospital-University of Padua (AOUP), and Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
[SDV] Life Sciences [q-bio], [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV]Life Sciences [q-bio], Models, Animal, Animals, Humans, Neuraminic Acids, Letters, Atherosclerosis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS, Mixed Function Oxygenases
Abstract

International audience

Published
2020

3. Generation of fertile cloned bull knock out for galactose-alpha 1,3-galactose and N-glycolylneuraminic acid antigens

Author

Perota, Andrea, Lagutina, Irina, Duchi, Roberto, Zanfrini, Elisa, Lazzari, Giovanna, Judor, Jean Paul, Conchon, Sophie, Bach, Jean-Marie, Bottio, Tomaso, Gerosa, Gino, Costa, Cristina, Galiñanes, Manuel, Roussel, Jean Christian, Padler-Karavani, Vered, Cozzi, Emanuele, Soulillou, Jean Paul, Galli, Cesare, Avantea Laboratory of Reproductive Technologies, Fondazione Avantea [Cremona, Italy], Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Nantes (UN), Immuno-Endocrinologie Cellulaire et Moléculaire, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Universita di Padova, IDIBELL--Hospital Universitari de Bellvitge, Vall d'Hebron University Hospital [Barcelona], Tel Aviv University [Tel Aviv], Transplant Immunology Unit, Universita degli Studi di Padova, European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013), ProdInra, Migration, Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID, Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Università degli Studi di Padova = University of Padua (Unipd), and Tel Aviv University (TAU)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

4. Generation of cattle knockout for galactose‐α1,3‐galactose and N‐glycolylneuraminic acid antigens

Author

Perota, Andrea, Lagutina, Irina, Duchi, Roberto, Zanfrini, Elisa, Lazzari, Giovanna, Judor, Jean Paul, Conchon, Sophie, Bach, Jean Marie, Bottio, Tomaso, Gerosa, Gino, Costa Farré, Cristina, Galiñanes, Manuel, Roussel, Jean Christian, Padler-Karavani, Vered, Cozzi, Emanuele, Soulillou, Jean Paul, Galli, Cesare, Universitat Autònoma de Barcelona, Avantea Laboratory of Reproductive Technologies [Cremona, Italy], Fondazione Avantea [Cremona, Italy], Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Immunoregulation And Immunointervention in Transplantation and Autoimmunity (Team 4 - U1064 Inserm - CRTI), 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 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), Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Department of Cardiac, Thoracic and Vascular Sciences and Public Health [Padova, Italy] (Cardiac Surgery Unit), Padova University School of Medicine [Padova, Italy] -Consorzio per la Ricerca Sanitaria - CORIS [Padova, Italy], Infectious Diseases and Transplantation Division [Barcelona, Spain], L’Hospitalet de Llobregat [Barcelona, Spain]-Bellvitge Biomedical Research Institute IDIBELL [Barcelona, Spain], Department of Cardiac Surgery & Reparative Therapy of the Heart [Barcelona, Spain], Vall d’Hebron Institute of Research [Barcelona, Spain]-Hospital Universitari Vall d'Hebron [Barcelona, Spain], Département de chirurgie thoracique et cardiovasculaire [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Cell Research and Immunology, Tel Aviv University [Tel Aviv], Transplantation Immunology Unit [Padua, Italy] (Department of Transfusion Medicine), University of Padua–Ospedale Giustinianeo [Padua, Italy], Le Bihan, Sylvie, Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Università degli Studi di Padova = University of Padua (Unipd)-Consorzio per la Ricerca Sanitaria - CORIS [Padova, Italy], Vall d'Hebron University Hospital [Barcelona]-Vall d’Hebron Research Institute (VHIR), Tel Aviv University (TAU), Università degli Studi di Padova = University of Padua (Unipd), and European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013)

Subjects
Male, 0301 basic medicine, knockout, Neu5Gc, 030230 surgery, Epitope, Mixed Function Oxygenases, law.invention, Animals, Genetically Modified, Gene Knockout Techniques, chemistry.chemical_compound, 0302 clinical medicine, Carn de boví, N-Glycolylneuraminic acid, law, xenotransplantation, Polymerase chain reaction, 2. Zero hunger, Sanger sequencing, Heart valves, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Immunogenicity, Galactosyltransferases, Vàlvules cardíaques, Heart Valve Prosthesis, symbols, bioprosthetic Heart Valve (BHV), Somatic cell nuclear transfer, Xenotransplantation, Female, Original Article, Beef, cattle, CMAH, GGTA1, αGal, Food Hypersensitivity, Knockout, Transplantation, Heterologous, Immunology, Biology, 03 medical and health sciences, symbols.namesake, Antigens, Heterophile, Cytidine Monophosphate, Animals, Humans, Gene, Bioprosthesis, Galactosyltransferase, Transplantation, Galactose, Original Articles, Fibroblasts, Bioprosthetic Heart Valve (BHV), Molecular biology, 030104 developmental biology, chemistry, Cattle, Neuraminic Acids, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Two well-characterized carbohydrate epitopes are absent in humans but present in other mammals. These are galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc) which are introduced by the activities of two enzymes including α(1,3) galactosyltransferase (encoded by the GGTA1 gene) and CMP-Neu5Gc hydroxylase (encoded by the CMAH gene) that are inactive in humans but present in cattle. Hence, bovine-derived products are antigenic in humans who receive bioprosthetic heart valves (BHVs) or those that suffer from red meat syndrome. Using programmable nucleases, we disrupted (knockout, KO) GGTA1 and CMAH genes encoding for the enzymes that catalyse the synthesis of αGal and Neu5Gc, respectively, in both male and female bovine fibroblasts. The KO in clonally selected fibroblasts was detected by polymerase chain reaction (PCR) and confirmed by Sanger sequencing. Selected fibroblasts colonies were used for somatic cell nuclear transfer (SCNT) to produce cloned embryos that were implanted in surrogate recipient heifers. Fifty-three embryos were implanted in 33 recipients heifers; 3 pregnancies were carried to term and delivered 3 live calves. Primary cell cultures were established from the 3 calves and following molecular analyses confirmed the genetic deletions. FACS analysis showed the double-KO phenotype for both antigens confirming the mutated genotypes. Availability of such cattle double-KO model lacking both αGal and Neu5Gc offers a unique opportunity to study the functionality of BHV manufactured with tissues of potentially lower immunogenicity, as well as a possible new clinical approaches to help patients with red meat allergy syndrome due to the presence of these xenoantigens in the diet.

Published
2019

5. Divergent selection on adrenocortical activity modulates immune traits in pig

Author

Lieubeau, Blandine, Hervé, Julie, Haurogné, Karine, Bacou, Elodie, Allard, Marie, Billon, Yvon, Terenina, Elena, Bach, Jean-Marie, Mormède, Pierre, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2018

6. Anti-gal and anti-neu5gc responses in non-immunosuppressed patients following treatment with anti-thymocyte globulin

Author

Salama, Apolline, Evanno, Gwénaëlle, Lim, Noha, Rousselot, Juliette, Le Berre, Ludmilla, Nicot, Arnaud, Bach, Jean-Marie, Brouard, Sophie, Harris, Kristina M., Ehlers, Mario R., Gitelman, Stephen E., Soulillou, Jean-Paul, Université de Nantes (UN), Xenothera [Nantes, France], Immune Tolerance Network, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Division of Pediatric Endocrinology and Diabetes, and Duke University [Durham]

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; Background Polyclonal antihuman thymocyte rabbit IgGs (antithymocyte globulin [ATG]) are popular immunosuppressive drugs used to prevent or treat organ or bone-marrow allograft rejection, graft versus host disease, and autoimmune diseases. However, animal-derived glycoproteins are also strongly immunogenic and rabbit ATG induces serum sickness disease in almost all patients without additional immunosuppressive drugs, as seen in the Study of Thymoglobulin to arrest Type 1 Diabetes (START) trial of ATG therapy in new-onset type 1 diabetes. Methods Using enzyme-linked immunosorbent assay, we analyzed serial sera from the START study to decipher the various anti-ATG specificities developed by the patients in this study: antitotal ATG, but also antigalactose-α1-3-galactose (Gal) and anti-Neu5Gc antibodies, 2 xenocarbohydrate epitopes present on rabbit IgG glycans and lacking in humans. Results We show that diabetic patients have substantial levels of preexisting antibodies of the 3 specificities, before infusion, but of similar levels as healthy individuals. ATG treatment resulted in highly significant increases of both IgM (for anti-ATG and anti-Neu5Gc) and IgG (for anti-ATG, -Gal, and -Neu5Gc), peaking at 1 month and still detectable 1 year postinfusion. Conclusions Treatment with rabbit polyclonal IgGs in the absence of additional immunosuppression results in a vigorous response against Gal and Neu5Gc epitopes, contributing to an inflammatory environment that may compromise the efficacy of ATG therapy. The results also suggest using IgGs lacking these major xenoantigens may improve safety and efficacy of ATG treatment.

Published
2017

7. Immune phenotype and IgG characteristics of Neu5Gc and alpha-1-3-gal double knock-out pigs

Author

Salama, Apolline, Conchon, Sophie, Perota, Andrea, Martinet, Bernard, Judor, Jean-Paul, Evanno, Gwénaëlle, Bernardet, Stéphanie Le-Bas, Le Berre, Ludmilla, Hervouet, Jeremy, Minault, David, Concordet, Jean-Paul, Dugast, Emilie, Vanhove, Bernard, Abadie, Jérôme, Gaide, Nicolas, Lagutina, Irina, Duchi, Roberto, Lazzari, Giovanna, Floch, Robert, Duvaux, Odile, Toutain, Pierre-Louis, Maillasson, Mike, Sachs, David H., Gauthier, Olivier, Brouard, Sophie, Cozzi, Emanuele, Blancho, Gilles, Perreault, Hélène, Bach, Jean-Marie, Galli, Cesare, Soulillou, Jean-Paul, Institut National de la Santé et de la Recherche Médicale (INSERM), Société d'Accélération du Transfert de Technologies (SATT OUEST VALORISATION), Fondazione Avantea, Partenaires INRAE, Xenothera [Nantes, France], Centre National de la Recherche Scientifique (CNRS), Animaux modèles pour la recherche en oncologie comparée (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Massachusetts General Hospital [Boston], University Hospital of Padua, Consortium for Research in Organ Transplantation (CORIT), University of Manitoba, University of Manitoba [Winnipeg], Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Department of Veterinary Medical Sciences, University of Bologna, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and ProdInra, Migration

Subjects
[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], [SDV.OT] Life Sciences [q-bio]/Other [q-bio.OT], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015

8. Increased late graft loss in kidney recipients with serum sickness disease following anti-thymocyte globulin induction: relation with an anti-NEU5GC response

Author

Salama, Apolline, Couvrat-Desvergnes, Gregoire, Le Berre, Ludmilla, Evanno, Gwenaelle, Viklicky, Ondrej, Hruba, Petra, Pavel Vesely, Guerif, Pierrick, Dejoie, Thomas, Nicot, Arnaud B., Bach, Jean-Marie, Brouard, Sophie, Castagnet, Stephanie, Giral, Magali, Harb, Jean, Foucher, Yohann, Lorent, Marine, Soulillou, Jean-Paul, Société d'Accélération du Transfert de Technologies (SATT OUEST VALORISATION), Institut National de la Santé et de la Recherche Médicale (INSERM), Transplant Center, Brno University of Technology [Brno] (BUT), Centre hospitalier universitaire de Nantes (CHU Nantes), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Etablissement Français du Sang, Biostatistique, Recherche Clinique et Mesures Subjectives en Santé, and Université de Nantes (UN)

Subjects
[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015

9. Characteristics of IgGs Produced in Neu5Gc and alpha 1-3 Gal Double Knock-Out Pigs

Author

Salama, A., Conchon, S., Perota, A., Martinet, B., Judor, J. -P., Evanno, G., Bernardet, S. Le-Bas, Le Berre, L., Hervouet, J., Minault, D., Concordet, J. -P., Dugast, E., Vanhove, B., Abadie, J., Gaide, N., Lagutina, I., Duchi, R., Lazzari, G., Sachs, D., Gauthier, O., Brouard, S., Cozzi, E., Blancho, G., Perreault, H., Bach, Jean-Marie, Galli, C., Soulillou, J. -P., ProdInra, Migration, Université de Nantes (UN), Société d'Accélération du Transfert de Technologies (SATT OUEST VALORISATION), Fondazione Avantea, Partenaires INRAE, Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Acides nucléiques : dynamique, ciblage, et fonctions biologiques - Régulation et dynamique des génomes (ANDCFB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Animaux modèles pour la recherche en oncologie comparée (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Fondazione Avantea [Cremona, Italy], Massachusetts General Hospital, Massachusetts General Hospital [Boston], University Hospital of Padua, University of Manitoba, University of Manitoba [Winnipeg], Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, and American Society of Transplant Surgeons (ASTS). Arlington, USA.

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015

10. Metronidazole and Hydroxymetronidazole Central Nervous System Distribution: 1. Microdialysis Assessment of Brain Extracellular Fluid Concentrations in Patients with Acute Brain Injury

Author

Salama, Apolline, Fichou, Nolwenn, Allard, Marie, Dubreil, Laurence, De Beaurepaire, Laurence, Viel, Alexis, Jegou, Dominique, Bosch, Steffi, Bach, Jean-Marie, Frasca, Denis, Dahyot-Fizelier, Claire, Adier, Christophe, Mimoz, Olivier, Debaene, Bertrand, Couet, William, Marchand, Sandrine, 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), Conservatoire Botanique National Méditerranéen de Porquerolles, Conservatoire National Botanique, HEC Montréal (HEC Montréal), Developpement et Pathologie du Tissu Musculaire (DPTM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Recherche Agronomique (INRA), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'anesthésie réanimation [Poitiers], Développement et Pathologie du Tissu Musculaire (DPTM), and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
Male, Microdialysis, [SDV]Life Sciences [q-bio], Central nervous system, Pharmacology, Blood–brain barrier, Cerebrospinal fluid, Anti-Infective Agents, In vivo, Metronidazole, Extracellular fluid, medicine, Humans, Distribution (pharmacology), Pharmacology (medical), Biotransformation, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, Aged, Chemistry, Brain, Extracellular Fluid, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Infectious Diseases, medicine.anatomical_structure, Blood-Brain Barrier, Area Under Curve, Brain Injuries, Anesthesia, medicine.drug
Abstract

The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC 0–τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 μg ml −1 . This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution.

Published
2014

11. Carbon monoxide-treated dendritic cells decrease β1-integrin induction on CD8 + T cells and protect from type 1 diabetes

Author

Simon, Thomas, Pogu, Sylvie, Tardif, Virginie, Rigaud, Kevin, Rémy, Severine, Piaggio, Eliane, Bach, Jean-Marie, Anegon, Ignacio, Blancou, Philippe, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de 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), Genetic and Cellular Engineering in Immunology and Regenerative Medicine (Team 2 - U1064 Inserm - CRTI), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Immunologie - Immunopathologie - Immunothérapie (I3), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Fondation Centaure, Fondation Progreffe. Grant Number: 5–2010‐640., Région Pays de la Loire through the core facility Research and Development for Clinical Transfer., Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Le Bihan, Sylvie, Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Integrin beta1, Autoreactive CD8+ T cells, Diabetes, Down-Regulation, β1-integrin, Mice, Transgenic, CD8-Positive T-Lymphocytes, Autoantigens, Dendritic cells, Coculture Techniques, Peptide Fragments, Disease Models, Animal, Mice, Diabetes Mellitus, Type 1, Cell Movement, Insulin-Secreting Cells, Immune Tolerance, Animals, Humans, Carbon monoxide, Pancreas, Cells, Cultured, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Carbon monoxide (CO) treatment improves pathogenic outcome of autoimmune diseases by promoting tolerance. However, the mechanism behind this protective tolerance is not yet defined. Here, we show in a transgenic mouse model for autoimmune diabetes that ex vivo gaseous CO (gCO)-treated DCs loaded with pancreatic β-cell peptides protect mice from disease. This protection is peptide-restricted, independent of IL-10 secretion by DCs and of CD4 + T cells. Although no differences were observed in autoreactive CD8 + T-cell function from gCO-treated versus untreated DC-immunized groups, gCO-treated DCs strongly inhibited accumulation of autoreactive CD8 + T cells in the pancreas. Interestingly , induction of β1-integrin was curtailed when CD8 + T cells were primed with gCO-treated DCs, and the capacity of these CD8 + T cells to lyse isolated islet was dramatically impaired. Thus, immunotherapy using CO-treated DCs appears to be an original strategy to control autoimmune disease.

Published
2013

13. The frequency and immunodominance of islet-specific CD8+ T-cell responses change after type 1 diabetes diagnosis and treatment

Author

Martinuzzi, Emanuela, Novelli, Giulia, Scotto, Matthieu, Blancou, Philippe, Bach, Jean-Marie, Chaillous, Lucy, Bruno, Graziella, Chatenoud, Lucienne, van Endert, Peter, Mallone, Roberto, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dipartimento di Medicina, Università degli studi di Torino = University of Turin (UNITO), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Clinique d'endocrinologie, and Mallone, Roberto

Subjects
TRANSGENIC MICE, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, endocrine system, IDENTIFICATION, [SDV.IMM] Life Sciences [q-bio]/Immunology, EPITOPES, PERIPHERAL-BLOOD, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, NOD MICE, INSULIN, GLUTAMIC-ACID DECARBOXYLASE, IA-2, ANTIBODY, ONSET, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International audience; OBJECTIVE: Islet-reactive CD8(+) T-cells play a key role in the pathogenesis of type 1 diabetes in the NOD mouse. The predominant T-cell specificities change over time, but whether similar shifts also occur after clinical diagnosis and insulin treatment in type 1 diabetic patients is unknown. RESEARCH DESIGN AND METHODS: We took advantage of a recently validated islet-specific CD8(+) T-cell gamma-interferon enzyme-linked immunospot (ISL8Spot) assay to follow responses against preproinsulin (PPI), GAD, insulinoma-associated protein 2 (IA-2), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) epitopes in 15 HLA-A2(+) adult type 1 diabetic patients close to diagnosis and at a second time point 7-16 months later. RESULTS: CD8(+) T-cell reactivities were less frequent at follow-up, as 28.6% of responses tested positive at type 1 diabetes diagnosis vs. 13.2% after a median of 11 months (P = 0.003). While GAD and IA-2 autoantibody (aAb) titers were unchanged in 75% of cases, the fraction of patients responding to PPI and/or GAD epitopes by ISL8Spot decreased from 60-67 to 20% (P < 0.02). The previously subdominant IA-2(206-214) and IGRP(265-273) peptides were newly targeted, thus becoming the immunodominant epitopes. CONCLUSIONS: Shifts both in frequency and in immunodominance of CD8(+) T-cell responses occur more rapidly than do changes in aAb titers. These different kinetics may suggest complementary clinical applications for T-cell and aAb measurements.

Published
2008

14. The frequency and immunodominance of islet-specific CD8+ T-cell responses change after type 1 diabetes diagnosis and treatment.: CD8+ T-cell responses change after type 1 diabetes onset

Author

Martinuzzi, Emanuela, Novelli, Giulia, Scotto, Matthieu, Blancou, Philippe, Bach, Jean-Marie, Chaillous, Lucy, Bruno, Graziella, Chatenoud, Lucienne, Van Endert, Peter, Mallone, Roberto, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dipartimento di Medicina, Università degli studi di Torino (UNITO), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Clinique d'endocrinologie, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Università degli studi di Torino ( UNITO ), Immuno-Endocrinologie Cellulaire et Moléculaire ( IECM ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Nantes ( UN ) -Ecole Nationale Vétérinaire de Nantes

Subjects
endocrine system, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, [SDV.IMM]Life Sciences [q-bio]/Immunology, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Abstract

International audience; OBJECTIVE: Islet-reactive CD8(+) T-cells play a key role in the pathogenesis of type 1 diabetes in the NOD mouse. The predominant T-cell specificities change over time, but whether similar shifts also occur after clinical diagnosis and insulin treatment in type 1 diabetic patients is unknown. RESEARCH DESIGN AND METHODS: We took advantage of a recently validated islet-specific CD8(+) T-cell gamma-interferon enzyme-linked immunospot (ISL8Spot) assay to follow responses against preproinsulin (PPI), GAD, insulinoma-associated protein 2 (IA-2), and islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) epitopes in 15 HLA-A2(+) adult type 1 diabetic patients close to diagnosis and at a second time point 7-16 months later. RESULTS: CD8(+) T-cell reactivities were less frequent at follow-up, as 28.6% of responses tested positive at type 1 diabetes diagnosis vs. 13.2% after a median of 11 months (P = 0.003). While GAD and IA-2 autoantibody (aAb) titers were unchanged in 75% of cases, the fraction of patients responding to PPI and/or GAD epitopes by ISL8Spot decreased from 60-67 to 20% (P < 0.02). The previously subdominant IA-2(206-214) and IGRP(265-273) peptides were newly targeted, thus becoming the immunodominant epitopes. CONCLUSIONS: Shifts both in frequency and in immunodominance of CD8(+) T-cell responses occur more rapidly than do changes in aAb titers. These different kinetics may suggest complementary clinical applications for T-cell and aAb measurements.

Published
2008

15. Myeloid derived suppressor cells recruited by cyclophosphamide in the spleen of non-obese diabetic mouse might participate to diabetes acceleration through their further migration and differentiation into the pancreas

Author

Caquard, Marylène, Ferret-Bernard, Stéphanie, Haurogne, Karine, Ouary, Michèle, Allard, Marie, Bach, Jean-Marie, Lieubeau-Teillet, Blandine, ESIM - Déterminants Sociaux de la Santé et du Recours aux Soins (DS3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), UMR 707A IECM, Ecole Nationale Vétérinaire de Nantes, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

absent

Published
2008

17. Effet de la protéine pdx1-vp16 sur la différenciation d'une lignée de cellules souches hépatiques en cellules insulino-sécrétrices

Author

Cuvelier Delisle, Juliette, Bosch, Steffi, Martignat, Lionel, Bach, Jean-Marie, Louzier, Vanessa, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
DIFFÉRENCIATION PANCRÉATIQUE ENDOCRINE, [SDV]Life Sciences [q-bio], DIABÈTE TYPE 1
Published
2007

18. Easy and rapid method of zygosity determination in transgenic mice by SYBR (R) Green real-time quantitative PCR with a simple data analysis

Author

Haurogne, Karine, Bach, Jean-Marie, Lieubeau-Teillet, Blandine, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes

Subjects
TRANSGENIC MICE, [SDV.GEN]Life Sciences [q-bio]/Genetics, REAL-TIME QUANTITATIVE PCR, ZYGOSITY, SYBR (R) GREEN
Abstract

International audience; Establishment and maintenance of transgenic mouse strains require being able to distinguish homozygous from heterozygous animals. To date, the developed real-time quantitative PCR techniques are often complicated, time-consuming and expensive. Here, we propose a very easy and rapid method with a simple data analysis to determine zygosity in transgenic mice. We show that the real-time quantitative PCR using SYBR (R) Green fluorescent dye can be applied to discriminate two-fold differences in copy numbers of the transgene. Our procedure has to fit only three simple requirements: (1) to design primers capable of detecting one Ct difference for two-fold differences in DNA amounts (2) to measure genomic DNA concentrations accurately and (3) to have a reference animal of known zygosity in each run. Then, if the Ct values for the control gene are similar in all samples, we are able to compare directly the Ct values for the transgene in every sample, and so, to deduce the zygosity status of each mouse relative to the reference animal. This method is really simple and reliable, and it may be valuable as a rapid screening tool for zygosity status in transgenic animals.

Published
2007

20. CD8+ T-Cell Responses Identify {beta}-Cell Autoimmunity in Human Type 1 Diabetes Diabetes

Author

Mallone, Roberto, Martinuzzi, Emanuela, Blancou, Philippe, Novelli, Giulia, Afonso, Georgia, Dolz, Manuel, Bruno, Graziella, Chaillous, Lucy, Chatenoud, Lucienne, Bach, Jean-Marie, Van Endert, Peter, Diabète de Type 1 : mécanismes et traitements immunologiques, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de Médecine, Université de Ngozi, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Universita di Torino, Clinique d'Endocrinologie, Institut du Thorax-Centre hospitalier universitaire de Nantes (CHU Nantes), ProdInra, Migration, and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV] Life Sciences [q-bio], GLUTAMIC-ACID DECARBOXYLASE, MONOCLONAL-ANTIBODY, IDENTIFICATION, [SDV]Life Sciences [q-bio], ONSET, IMMUNE-RESPONSE, ASSAYS, PERIPHERAL-BLOOD, NOD MICE, INSULIN, DISEASE
Abstract

International audience; Despite the understanding that type 1 diabetes pathogenesis is mediated by T-cells, detection of these rare lymphocytes remains largely elusive. Suitable T-cell assays are highly needed, since they could offer preclinical diagnoses and immune surrogate end points for clinical trials. Although CD4+ T-cell assays have met with limited success, CD8+ T-cells are increasingly recognized as key actors in the diabetes of the NOD mouse. CD8+ T-cells are likely to play a role also in humans and may provide new markers of β-cell autoimmunity. Taking advantage of a panel of HLA-A2–restricted β-cell epitopes derived from preproinsulin, GAD, and islet glucose-6-phosphatase catalytic subunit-related protein (IGRP), we have implemented an islet-specific CD8+ T-cell interferon-γ enzyme-linked immunospot (ISL8Spot) assay. The ISL8Spot assay is capable of detecting and quantifying β-cell–reactive CD8+ T-cells directly ex vivo, without any preliminary expansion, using either fresh or frozen samples. Positive ISL8Spot responses separate new-onset diabetic and healthy samples with high accuracy (86% sensitivity, 91% specificity), using as few as five immunodominant epitopes. Moreover, sensitivity reaches 100% when the ISL8Spot assay is complemented by antibody determinations. Combination of CD8+ T-cell measurements with immune intervention strategies may open new avenues toward type 1 diabetes prediction and prevention.

Published
2007

21. Caractérisation des cellules dendritiques canines différenciées à partir des monocytes du sang périphérique

Author

Ibisch, Catherine, Lieubeau, Blandine, Pradal, Gilbert, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Université de Nantes (UN), and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
ULTRASTRUCTURE, CELLULE DENDRITIQUE, [SDV]Life Sciences [q-bio], CULTURE CELLULAIRE, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2006

22. HLA-A2 restricted islet-reactive CD8+ T-cells in type 1 diabetes

Author

Blancou, Philippe, Sévère, Sabine, Pogu, Sylvie, Haurogne, Karine, Van Endert, PM, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Inconnu

Subjects
[SDV]Life Sciences [q-bio]
Published
2006

23. HLA-A2-restricted islet-reactive CD8+ T-cells in type 1 diabetes

Author

Blancou, Philippe, Mallone, R, Martinuzzi, E, Sévère, Sabine, Pogu, Sylvie, Haurogné, Karine, Van Endert, P, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Inconnu

Subjects
[SDV]Life Sciences [q-bio]
Published
2006

24. Lymphocytic insulitis in a dog with juvenile diabetes mellitus

Author

Jouvion, Gregory, Abadie, Jérôme, Bach, Jean-Marie, Roux, F, Miclard, J, Deschamps, Jack-Yves, Guigand, Lydie, Saï, Pierre, WYERS, Monique, Inconnu, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Développement et Pathologie du Tissu Musculaire (DPTM), and Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes

Subjects
[SDV]Life Sciences [q-bio]
Published
2006

25. Functional canine dendritic cells generated in vitro from peripheral blood mononuclear cells (PBMC) : Structural and functional characterization

Author

Ibisch, Catherine, Bach, Jean-Marie, Lieubeau, Blandine, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio], IMMUNOLOGIE, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2005

26. CD8+ T Lymphocytes Specific to GAD65 could mediate autoimmune diabetes in NOD mouse

Author

Sévère, Sabine, Gauvrit, Anne, Vu, Anh Tuan, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
LYMPHOCYTE, AUTOIMMUNE DIABETE, [SDV]Life Sciences [q-bio], IMMUNOLOGIE
Published
2005

27. Myeloid suppressor cell (MSC) deficiencies in non-obese diabetic (NOD) mice: a role in type 1 diabetes pathogenesis ?

Author

Ferret-Bernard, Stéphanie, Allard, Marie, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
obésité, [SDV]Life Sciences [q-bio], souris, lymphocyte, MYELOID SUPPRESSOR CELL, mus musculus, diabète
Abstract

absent

Published
2004

28. Identification and characterization of diabetogenic CD8+ T-cells specific of 65 kDa glutamic acid decarboxylase (GAD65) using DNA immunization in non-obese diabetic (NOD) mouse

Author

Sévère, Sabine, Gauvrit, Anne, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
NON OBESE DIABETIC, PLASMID IMMUNIZATION, GLUTAMIC ACID DECARBOXYLASE, [SDV]Life Sciences [q-bio]
Published
2004

31. Ultrastructural markers expressed in cultured canine dendritic cells and laminated bodies found in Langerhans cells : similarities and differences

Author

Ibisch, Catherine, Lieubeau, Blandine, Pradal, Gilbert, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Université de Nantes (UN), and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes

Subjects
LYMPHOCYTE, LANGERHANS CELL, [SDV]Life Sciences [q-bio], DENDRITIC CELL, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2004

32. Myeloid suppressor cell (MSC) deficiencies in non-obese diabetic (NOD) mice: a role in type 1 diabetes pathogenesis ?

Author

Ferret-Bernard, Stéphanie, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

absent

Published
2004

33. Mise au point d’un modèle de diabète insulinodépendant chez le chien

Author

Joussemet, Béatrice, Saï, Pierre, Bach, Jean-Marie, Inconnu, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio]
Published
2004

34. Inhibitory macrophage deficiency in NOD mice : a role in type 1 diabetes pathogenesis ?

Author

Ferret-Bernard, Stéphanie, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
NON OBESE DIABETIC, [SDV]Life Sciences [q-bio], MACROPHAGE, DENDRITIC CELL
Abstract

absent

Published
2003

35. Déficience des iMacs chez la souris NOD : implication dans le diabète autoimmun ?

Author

Ferret-Bernard, Stéphanie, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio], DIABÈTE TYPE 1
Abstract

absent

Published
2003

37. GAD peptide vaccines for T1DM : not just a blueprint ?

Author

Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), and Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA)

Subjects
DIABETE TYPE 1, AUTOIMMUNE DISEASE, NON OBESE DIABETE, [SDV]Life Sciences [q-bio]
Abstract

DMCCAD Stockholm Sweden June 2003

Published
2003

38. Génération de iMacs in vitro à partir de progéniteurs hématopoïétique de souris

Author

Ferret-Bernard, Stéphanie, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
immunosuppression, [SDV]Life Sciences [q-bio], iMacs, progenitors
Abstract

Notre étude précise l'origine myéloïde des iMacs et fournit une méthode relativement simple pour générer in vitro des iMacs fonctionnels à partir de progéniteurs hématopoïétiques murins.

Published
2002

39. Déficience des iMacs chez la souris Nod : implication dans le diabète autoimmun ?

Author

Ferret-Bernard, Stéphanie, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

Les iMacs de souris NOD présentent des déficiences de maturation et de fonction. Ces anomalies pourraient être impliquées dans la progression du TID induit par CyP.

Published
2002

40. iMacs deficiency in NOD mice: implication in cyclophosphamide-induced diabetes?

Author

Ferret-Bernard, Stéphanie, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

Background and aims: The role of dendritic cells and macrophages in pancreatic beta-cell destruction in type I diabetes, remains unclear. NOD mice displays functional dendritic cell abnormalities which could be involved in self-tolerance break-down to beta-cell antigens. A peculiar set of macrophages, CD11b+Gr-1+ inhibitory macrophages (iMacs), is implicated in profound depression of CD8 T-cell functions sometimes observed in tumor growth, treatment with cyclophosphamide (CyP) and overwhelming infections. iMacs could trigger apoptotic death of T-lymphocytes through a secretion of NO, and may be involved in the control of T-cell expansion. The aim of our study was to characterize the phenotype of iMacs in NOD mice and to investigate their possible role in diabetes pathogenesis.Materials and methods: iMacs were obtained either (1) after a 6 day-culture of lin- c-kit+ hematopoietic progenitor cells (HPC) with GM-CSF, SCF and TNF-alpha or (2) by purification from spleens of mice treated with low doses of CyP (100mg/kg, three times at three-day intervals).Results: Compared to HPC from BALB/c and C57BL/6 mice, NOD-HPC were unable to differentiate into iMacs (p

Published
2002

41. Caractérisation d'un défaut de maturation et d'une déficience fonctionnelle des iMacs chez la souris NOD : implication dans la pathogénie du diabète de type 1 ?

Author

Ferret-Bernard, Stéphanie, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes

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

absent

Published
2002

42. Défaut de maturation et déficience fonctionnelle des iMACS chez la souris NOD : implication dans la pathogénie du diabète de type 1 ?

Author

Ferret-Bernard, Stéphanie, Saï, Pierre, Bach, Jean-Marie, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, and Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)

Subjects
DIABETE DE TYPE 1, [SDV]Life Sciences [q-bio], Tolérance périphérique, cellule, souris, mus musculus, iMacs
Abstract

absent

Published
2002

43. Neu5Gc and α1-3 GAL Xenoantigen Knockout Does Not Affect Glycemia Homeostasis and Insulin Secretion in Pigs

Author

Andrea Perota, Pierre Weiss, Nicolas Gaide, Steffi Bosch, Anne Moure, Jean-Paul Concordet, Emanuele Cozzi, Mathilde Mosser, Cesare Galli, Jérôme Guicheux, Jeremy Hervouet, David Minault, Jean-Marie Bach, Jean-Paul Soulillou, Jérôme Abadie, Sylvie Pogu, Apolline Salama, Xavier Lévêque, Olivier Gauthier, Dominique Jégou, Roberto Duchi, Gilles Blancho, Jean-Paul Judor, Sophie Brouard, Stéphanie Le Bas-Bernardet, Giovanna Lazzari, Ludmilla Le Berre, Sophie Conchon, David Riochet, Corentin Danna, Irina Lagutina, 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), Immuno-Endocrinologie Cellulaire et Moléculaire [Nantes] (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Société d'Accélération du Transfert de Technologies (SATT OUEST VALORISATION), Avantea Laboratory of Reproductive Technologies, Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Animaux Modèles pour la Recherche en Oncologie [Nantes] (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Muséum national d'Histoire naturelle (MNHN), Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-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), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), PHU 4 OTONN, Centre hospitalier universitaire de Nantes (CHU Nantes), CIC - Nantes, Avantea Foundation, Transplantation Immunology Unit, Universita degli Studi di Padova, Consortium for Research in Organ Transplantation (CORIT), University of Bologna, Université de Nantes (UN), Avantea Laboratory of Reproductive Technologies [Cremona, Italy], Département de Chirurgie Expérimentale [Nantes] (Oniris - Centre de recherche et d'investigation préclinique), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre de recherche et d'investigation préclinique [Nantes], Museum National d'Histoire Naturelle de Paris, Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Département de pédiatrie [CHU Nantes], Université de Nantes - UFR Odontologie, Ostéo-articulaire - Tête et cou - Odontologie - Neurochirurgie - Neurotraumatologie [CHU Nantes] (Pôle hospitalo-universitaire PHU4 - OTONN), CIC biothérapies CBT 0503 [Nantes], Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Avantea Foundation [Cremona, Italy], Transplantation Immunology Unit [Padua, Italy] (Department of Transfusion Medicine), University of Padua–Ospedale Giustinianeo [Padua, Italy], Consortium for Research in Organ Transplantation [Padua, Italy] (CORIT), Department of Veterinary Medical Sciences [Ozzano dell'Emilia, Italy], Pays de la Loire Region (France) (Xenothera academic program and to A.S.), the Société d’Accélération du Transfert de Technologies Ouest Valorisation (to A.S.)., ANR: ANR-10IBHU-005, ANR: ANR-II-INSB-0014, European Project: LSHB-CT-2006-037377, European Project: 603049, European Project: ECTIS, Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de la Recherche Agronomique (INRA), Animaux modèles pour la recherche en oncologie comparée (AMaROC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Muséum national d'Histoire naturelle (MNHN), Institut de Transplantation Urologie Néphrologie, AMaROC - Oniris Nantes, Centre d'Investigation Clinique (CIC) Biotherapy, This work was supported by Pays de la Loire Region (France) (Xenothera academic program and to A.S.), the Société d’Accélération du Transfert de Technologies Ouest Valorisation (to A.S.), the European Center for Transplantation and Immunotherapy Sciences (ECTIS IHU, Nantes, France), the National Research Agency 'Investment Into The Future' programs (ANR-10-IBHU-005, to X.L., and ANR-II-INSB-0014), the European Commission’s Xenome Sixth Framework Programme (LSHB-CT-2006-037377), and the European Seventh Framework Programme 'Translink' research program (grant agreement 603049 and to L.L.B.)., ANR-10-IBHU-0005,CESTI (TSI-IHU),Centre Européen des Sciences de la Transplantation et de l'Immunothérapie (TSI-IHU)(2010), ANR-11-INBS-0014,TEFOR,Transgenèse pour les Etudes Fonctionnelles sur les Organismes modèles(2011), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Padova = University of Padua (Unipd), Consorzio per la Ricerca sul Trapianto d'Organ = Consortium for Research in Organ Transplantation (CORIT), University of Bologna/Università di Bologna, European Project: 603049,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,TRANSLINK(2013), Mosser, Mathilde, Lévêque, Xavier, Perota, Andrea, Galli, Cesare, Soulillou, Jean-Paul, Bach, Jean-Marie, Jehan, Frederic, 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, Infrastructures - Transgenèse pour les Etudes Fonctionnelles sur les Organismes modèles - - TEFOR2011 - ANR-11-INBS-0014 - INBS - VALID, and Defining the role of xeno-directed and autoimmune events in patients receiving animal-derived bioprosthetic heart valves - TRANSLINK - - EC:FP7:HEALTH2013-09-01 - 2017-08-31 - 603049 - VALID

Subjects
Blood Glucose, Male, 0301 basic medicine, Swine, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Islets of Langerhans Transplantation, 030230 surgery, Gene Knockout Techniques, 0302 clinical medicine, Insulin Secretion, Homeostasis, Insulin, Glucose homeostasis, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Heterologous, geography.geographical_feature_category, [SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, C-Peptide, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Islet, 3. Good health, Heterophile, medicine.anatomical_structure, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Type 1, medicine.medical_specialty, endocrine system, Transplantation, Heterologous, Animals, Antigens, Heterophile, Diabetes Mellitus, Type 1, Galactose, Glucagon, Glucose, Islets of Langerhans, Neuraminic Acids, Pancreas, Purinergic P1 Receptor Antagonists, Theophylline, Carbohydrate metabolism, Biology, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Diabetes Mellitus, Internal Medicine, medicine, Antigens, Transplantation, Type 1 diabetes, geography, Pancreatic islets, medicine.disease, 030104 developmental biology, Endocrinology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Xenocell therapy from neonate or adult pig pancreatic islets is one of the most promising alternatives to allograft in type 1 diabetes for addressing organ shortage. In humans, however, natural and elicited anti-bodies specific for pig xenoantigens, α-(1,3)-galactose (GAL) and N-glycolylneuraminic acid (Neu5Gc), are likely to significantly contribute to xenoislet rejection. We obtained double-knockout (DKO) pigs lacking GAL and Neu5Gc. Because Neu5Gc 2/2 mice exhibit glycemic dys-regulations and pancreatic b-cell dysfunctions, we evaluated islet function and glucose metabolism regulation in DKO pigs. Isolation of islets from neonate piglets yielded identical islet equivalent quantities to quantities obtained from control wild-type pigs. In contrast to wild-type islets, DKO islets did not induce anti-Neu5Gc antibody when grafted in cytidine monophosphate-N-acetylneuraminic acid hydroxylase KO mice and exhibited in vitro normal insulin secretion stimulated by glucose and theophylline. Adult DKO pancreata showed no histological abnormalities , and immunostaining of insulin and glucagon was similar to that from wild-type pancreata. Blood glucose, insulin, C-peptide, the insulin-to-glucagon ratio, and HOMA-insulin resistance in fasted adult DKO pigs and blood glucose and C-peptide changes after intravenous glucose or insulin administration were similar to wild-type pigs. This first evaluation of glucose homeostasis in DKO pigs for two major xenoantigens paves the way to their use in (pre)clinical studies.

Published
2017

44. Anti-EBOV GP IgGs Lacking α1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected Guinea Pigs

Author

Odile Duvaux, Andrea Perota, Hélène Perreault, Elsa Lheriteau, Bernard Martinet, Irina Lagutina, Gwénaëlle Evanno, Ludmilla Le Berre, Hervé Raoul, Olivier Reynard, Cesare Galli, Giovanna Lazzari, Apolline Salama, Frédéric Jacquot, Roberto Duchi, Sophie Conchon, Jean-Paul Judor, Viktor E. Volchkov, Jean-Marie Bach, Jean-Paul Soulillou, Hoa Le Mai, Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity (BMPV), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS 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)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire P4 - Jean Mérieux, Centre Européen de Virologie/Immunologie-Institut National de la Santé et de la Recherche Médicale (INSERM), Xenothera [Nantes, France], 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), Centre hospitalier universitaire de Nantes (CHU Nantes), Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Ecole Nationale Vétérinaire de Nantes-Université de Nantes (UN)-Institut National de la Recherche Agronomique (INRA), Avantea Laboratory of Reproductive Technologies [Cremona, Italy], University of Manitoba [Winnipeg], Anti-EBOV GP IgGs Lacking alpha 1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected Guinea Pigs, Reynard, Olivier, Jacquot, Frédéric, Evanno, Gwénaëlle, Mai, Hoa Le, Salama, Apolline, Martinet, Bernard, Duvaux, Odile, Bach, Jean-Marie, Conchon, Sophie, Judor, Jean-Paul, Perota, Andrea, Lagutina, Irina, Duchi, Roberto, Lazzari, Giovanna, Le Berre, Ludmilla, Perreault, Hélène, Lheriteau, Elsa, Raoul, Hervé, Volchkov, Viktor, Galli, Cesare, Soulillou, Jean-Paul, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Davoine, Laure-Hélène, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-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)-École normale supérieure de Lyon (ENS de Lyon)-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), Bases moléculaires de la pathogénicité virale – Molecular Basis of Viral Pathogenicity, Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, University of Manitoba, and University of Bologna

Subjects
0301 basic medicine, Male, Physiology, Swine, lcsh:Medicine, medicine.disease_cause, Antibodies, Viral, Biochemistry, Epitope, Immunoglobulin G, 0302 clinical medicine, Viral Envelope Proteins, Pig Models, Intraperitoneal Injections, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immune Physiology, Medicine and Health Sciences, 030212 general & internal medicine, Viral, Enzyme-Linked Immunoassays, lcsh:Science, Routes of Administration, Mammals, Multidisciplinary, Immune System Proteins, Immunogenicity, Vaccination, Agriculture, Animal Models, Hematology, Viral Load, Ebolavirus, 3. Good health, Antibodies, Anti-Idiotypic, Body Fluids, Titer, Blood, Anti-Idiotypic, Vertebrates, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Ebola, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, Anatomy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, Viral load, Research Article, EBOV, Livestock, Immunology, Guinea Pigs, α1-3-Galactose, Biology, rabbit antithymocyte globulin, hemorrhagic-fever, virus-infection, nonhuman-primates, sialic-acid, molecular characterization, monoclonal-antibody, immunoglobulin-g, disease, immunotherapy, Research and Analysis Methods, Rodents, Virus, Antibodies, 03 medical and health sciences, Model Organisms, medicine, Animals, Antigens, Ebola Vaccines, Immunoassays, Pharmacology, Ebola virus, lcsh:R, Organisms, Biology and Life Sciences, Proteins, Galactose, Anti-EBOV, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Hemorrhagic Fever, Ebola, Guinea pig, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, Amniotes, biology.protein, Immunologic Techniques, Hemorrhagic Fever, lcsh:Q, Neuraminic Acids
Abstract

International audience; Polyclonal xenogenic IgGs, although having been used in the prevention and cure of severe infectious diseases, are highly immunogenic, which may restrict their usage in new applications such as Ebola hemorrhagic fever. IgG glycans display powerful xenogeneic antigens in humans, for example α1-3 Galactose and the glycolyl form of neuraminic acid Neu5Gc, and IgGs deprived of these key sugar epitopes may represent an advantage for passive immunotherapy. In this paper, we explored whether low immunogenicity IgGs had a protective effect on a guinea pig model of Ebola virus (EBOV) infection. For this purpose, a double knock-out pig lacking α1-3 Galactose and Neu5Gc was immunized against virus-like particles displaying surface EBOV glycoprotein GP. Following purification from serum, hyper-immune polyclonal IgGs were obtained, exhibiting an anti-EBOV GP titer of 1:100,000 and a virus neutralizing titer of 1:100. Guinea pigs were injected intramuscularly with purified IgGs on day 0 and day 3 post-EBOV infection. Compared to control animals treated with IgGs from non-immunized double KO pigs, the anti-EBOV IgGs-treated animals exhibited a significantly prolonged survival and a decreased virus load in blood on day 3. The data obtained indicated that IgGs lacking α1-3 Galactose and Neu5Gc, two highly immunogenic epitopes in humans, have a protective effect upon EBOV infection.

Published
2016

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