Author: "Marie-Christine Vantyghem" / Publisher: hal ccsd - Searchworks@Jio Institute Digital Library Search Results

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23 results on '"Marie-Christine Vantyghem"'

1. Enhanced cell viscosity: a new phenotype associated with lamin A/C alterations

Author: Cécile Jebane, Alice-Anaïs Varlet, Marc Karnat, Lucero M. Hernandez-Cedillo, Amélie Lecchi, Frédéric Bedu, Camille Desgrouas, Corinne Vigouroux, Marie-Christine Vantyghem, Annie Viallat, Jean-François Rupprecht, Emmanuèle Helfer, Catherine Badens, Centre Interdisciplinaire de Nanoscience de Marseille (CINaM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Turing Centre for Living Systems [Marseille] (TCLS), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physique Théorique - UMR 7332 (CPT), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Génétique Médicale et Génomique Fonctionnelle (GMGF), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Amidex A-M-AAP-ID-17-66-170301-11.30
Subjects: [PHYS]Physics [physics], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft]
Abstract: Lamin A/C is a well-established key contributor to nuclear stiffness and its role in nucleus mechanical properties has been extensively studied. However, its impact on whole cell mechanics has been poorly addressed, even less so in terms of measurable physical parameters. In the present study, microfluidic experiments combined with theoretical analyses were performed to provide a quantitative estimation of the whole cell mechanical properties. This allowed the characterization of mechanical cell changes induced by lamin A/C alterations resulting from Atazanavir treatment or lipodystrophy-associated LMNA R482W pathogenic variant. Results unveil an increase in the long-time viscosity as a signature of cells affected by lamin A/C alterations. In addition, they show that the whole cell response to mechanical stress is driven not only by the nucleus but also by the nucleo-cytoskeleton links and the microtubule network. This enhanced cell viscosity assessed by our microfluidic device could represent a useful diagnosis marker for lamin-related diseases.
Published: 2023

2. Identification of predictive criteria for pathogenic variants of primary bilateral macronodular adrenal hyperplasia (PBMAH) gene ARMC5 in 352 unselected patients

Author: Lucas Bouys, Anna Vaczlavik, Anne Jouinot, Patricia Vaduva, Stéphanie Espiard, Guillaume Assié, Rossella Libé, Karine Perlemoine, Bruno Ragazzon, Laurence Guignat, Lionel Groussin, Léopoldine Bricaire, Isadora Pontes Cavalcante, Fidéline Bonnet-Serrano, Hervé Lefebvre, Marie-Laure Raffin-Sanson, Nicolas Chevalier, Philippe Touraine, Christel Jublanc, Camille Vatier, Gérald Raverot, Magalie Haissaguerre, Luigi Maione, Matthias Kroiss, Martin Fassnacht, Sophie Christin-Maitre, Eric Pasmant, Françoise Borson-Chazot, Antoine Tabarin, Marie-Christine Vantyghem, Martin Reincke, Peter Kamenicky, Marie-Odile North, Jérôme Bertherat, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancer et génome: Bioinformatique, biostatistiques et épidémiologie d'un système complexe, Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], CHU Lille, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Rouen, Normandie Université (NU), Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), 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), Hospices Civils de Lyon (HCL), Hôpital Haut-Lévêque - CHU de Bordeaux (Centre médico chirurgical Magellan), Physiologie et physiopathologie endocriniennes (PHYSENDO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), University Hospital of Würzburg, Klinikum der Universität [München], CHU Saint-Antoine [AP-HP], L B is recipient of research fellowships from the Cancer Research for Personalized Medicine (CARPEM) and the Fondation ARC pour la Recherche contre le Cancer, J B laboratory is supported by the Agence Nationale pour la Recherche grant ANR-18-CE14-0008-01 and the Fondation pour la Recherche Médicale (EQU201903007854). P T, C J, M F, S C M, F B C, M R, P C and J B clinical departments are part the European Reference Network on Rare Endocrine Conditions (Endo-ERN) – Project ID No 739572, and ANR-18-CE14-0008,STEROMICS,Steroïdogénomique de l'hypersécrétion des stéroïdes surrénaliens(2018)
Subjects: Armadillo Domain Proteins, Hyperplasia, Hydrocortisone, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 71 ARMC5, General Medicine, genetic screening, PBMAH, Endocrinology, Primary Bilateral Macronodular Adrenal Hyperplasia, adrenal tumors, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Adrenal Glands, Humans, Cushing syndrome, tumor suppressor gene, Retrospective Studies
Abstract: Objective Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a heterogeneous disease characterized by adrenal macronodules and variable levels of cortisol excess, with not clearly established clinical diagnostic criteria. It can be caused by ARMC5 germline pathogenic variants. In this study, we aimed to identify predictive criteria for ARMC5 variants. Methods We included 352 consecutive index patients from 12 European centers, sequenced for germline ARMC5 alteration. Clinical, biological and imaging data were collected retrospectively. Results 52 patients (14.8%) carried ARMC5 germline pathogenic variants and showed a more distinct phenotype than non-mutated patients for cortisol excess (24-h urinary free cortisol 2.32 vs 1.11-fold ULN, respectively, P < 0.001) and adrenal morphology (maximal adrenal diameter 104 vs 83 mm, respectively, P < 0.001) and were more often surgically or medically treated (67.9 vs 36.8%, respectively, P < 0.001). ARMC5-mutated patients showed a constant, bilateral adrenal involvement and at least a possible autonomous cortisol secretion (defined by a plasma cortisol after 1 mg dexamethasone suppression above 50 nmol/L), while these criteria were not systematic in WT patients (78.3%). The association of these two criteria holds a 100% sensitivity and a 100% negative predictive value for ARMC5 pathogenic variant. Conclusion We report the largest series of index patients investigated for ARMC5 and confirm that ARMC5 pathogenic variants are associated with a more severe phenotype in most cases. To minimize negative ARMC5 screening, genotyping should be limited to clear bilateral adrenal involvement and autonomous cortisol secretion, with an optimum sensitivity for routine clinical practice. These findings will also help to better define PBMAH diagnostic criteria.
Published: 2023

3. Cardiovascular complications of lipodystrophic syndromes – focus on laminopathies

Author: Isabelle Jéru, Marie-Christine Vantyghem, Héléna Mosbah, Karim Wahbi, Camille Vatier, B. Donadille, Corinne Vigouroux, Franck Boccara, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Filière Neuromusculaire (FILNEMUS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Cardiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de Référence des Pathologies Rares de l'Insulino-Sécrétion et de l'Insulino-Sensibilité [CHu Saint-Antoine] (PRISIS), Service de Cardiologie [CHU Saint-Antoine], Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: medicine.medical_specialty, Lipodystrophy, Endocrinology, Diabetes and Metabolism, LMNA, MESH: Laminopathies, MESH: Phenotype, Electrocardiography, Endocrinology, MESH: Lipodystrophy, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, Cardiovascular complications, MESH: Syndrome, Intensive care medicine, ComputingMilieux_MISCELLANEOUS, Focus (computing), MESH: Humans, business.industry, Laminopathies, MESH: Cardiovascular Diseases, General Medicine, Syndrome, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH: Electrocardiography, Phenotype, Cardiovascular Diseases, business
Abstract: International audience
Published: 2021

4. Rare causes of hypoglycemia in adults

Author: Claire Douillard, Marie-Christine Vantyghem, Arnaud Jannin, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
Subjects: endocrine system diseases, Fasting Hypoglycemia, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Hereditary fructose intolerance, [SDV]Life Sciences [q-bio], Type B insulin resistance, 0302 clinical medicine, Endocrinology, Risk Factors, Insulin receptor mutation, Age of Onset, Child, IGF2, NICTH, Fasting, General Medicine, 3. Good health, [SDV] Life Sciences [q-bio], Beta-oxidation disorders, 030220 oncology & carcinogenesis, Glycogen synthesis disorder, Postprandial Hypoglycemia, Adult, medicine.medical_specialty, Anti-insulin receptor and insulin antibodies, 030209 endocrinology & metabolism, Inborn errors of metabolism, Hypoglycemia, Diabetes Complications, 03 medical and health sciences, Neoglucogenesis disorders, Antigens, CD, Hyperinsulinism, Internal medicine, Diabetes mellitus, medicine, Humans, business.industry, Insulin, medicine.disease, Receptor, Insulin, Pancreatic Neoplasms, Glucokinase mutation, HIRATA syndrome, Congenital hyperinsulinism, Insulinoma, business, Metabolism, Inborn Errors
Abstract: International audience; Hypoglycemia is defined by a low blood glucose level associated to clinical symptoms. Hypoglycemia may be related to treatment of diabetes, but also to drugs, alcohol, critical illness, cortisol insufficiency including hypopituitarism, insulinoma, bariatric or gastric surgery, pancreas transplantation or glucagon deficiency, or may be surreptitious. Some hypoglycemic episodes remain unexplained, and genetic, paraneoplastic and immune causes should be considered. Genetic causes may be related to endogenous hyperinsulinism and to inborn errors of metabolism (IEM). Endogenous hyperinsulinism is related to monogenic congenital hyperinsulinism, and especially to mutations of the glucokinase-activating gene or of insulin receptors, both characterised by postprandial hypoglycemia with major hyperinsulinism. In adulthood, IEM-related hypoglycemia can persist in a previously diagnosed childhood disease or may be a presenting sign. It is suggested by systemic involvement (rhabdomyolysis after fasting or exercising, heart disease, hepatomegaly), sometimes associated to a family history of hypoglycemia. The timing of hypoglycemic episodes with respect to the last meal also helps to orientate diagnosis. Fasting hypoglycemia may be related to type 0, I or III glycogen synthesis disorder, fatty acid oxidation or gluconeogenesis disorder. Postprandial hypoglycemia may be related to inherited fructose intolerance. Exercise-induced hyperinsulinism is mainly related to activating mutation of the SLC16A1 gene. Besides exceptional ectopic insulin secretion, paraneoplastic causes involve NICTH (Non-Islet-Cell Tumour Hypoglycemia), caused by Big-IGF2 secretion by a large tumour, with low blood levels of insulin, C-peptide and IGF1. Autoimmune causes involve antibodies against insulin (HIRATA syndrome), especially in case of Graves' disease, or against the insulin receptor. Medical history, timing, and insulin level orientate the diagnosis.
Published: 2020

5. Looking at New Unexpected Disease Targets in LMNA-Linked Lipodystrophies in the Light of Complex Cardiovascular Phenotypes: Implications for Clinical Practice

Author: Stéphane Ederhy, Elisabeth Sarrazin, B. Donadille, Olivier Lascols, Fabien Picard, Bruno Fève, Isabelle Jéru, Corinne Vigouroux, Karim Wahbi, Camille Vatier, Ariel Cohen, Héléna Mosbah, Sophie Benabbou, Pascale Richard, Sophie Christin-Maitre, Marie-Christine Vantyghem, B. Neraud, Alban Redheuil, Jocelyn Inamo, Franck Boccara, 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU de la Martinique [Fort de France], Hôpital Pierre Zobda-Quitman [CHU de la Martinique], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [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)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Foch [Suresnes], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Filière Neuromusculaire (FILNEMUS), Institut de cardiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire d'Imagerie Biomédicale [Paris] (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Service de Cardiologie [CHU Saint-Antoine], Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité Fonctionnelle de Cardiogénétique et Myogénétique Moléculaire et Cellulaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Service de Biochimie Métabolique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Imagerie Biomédicale (LIB), Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Gestionnaire, Hal Sorbonne Université, and Service de Radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière]
Subjects: 0301 basic medicine, medicine.medical_specialty, lipodystrophy, [SDV]Life Sciences [q-bio], Cardiomyopathy, LMNA, 030204 cardiovascular system & hematology, Progeroid syndromes, 03 medical and health sciences, 0302 clinical medicine, lmna, cardiovascular disease, Internal medicine, medicine, lcsh:QH301-705.5, Coronary atherosclerosis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Generalized lipodystrophy, Partial Lipodystrophy, Dilated cardiomyopathy, General Medicine, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, lcsh:Biology (General), Cardiology, Lipodystrophy, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Variants in LMNA, encoding A-type lamins, are responsible for laminopathies including muscular dystrophies, lipodystrophies, and progeroid syndromes. Cardiovascular laminopathic involvement is classically described as cardiomyopathy in striated muscle laminopathies, and arterial wall dysfunction and/or valvulopathy in lipodystrophic and/or progeroid laminopathies. We report unexpected cardiovascular phenotypes in patients with LMNA-associated lipodystrophies, illustrating the complex multitissular pathophysiology of the disease and the need for specific cardiovascular investigations in affected patients. A 33-year-old woman was diagnosed with generalized lipodystrophy and atypical progeroid syndrome due to the newly identified heterozygous LMNA p.(Asp136Val) variant. Her complex cardiovascular phenotype was associated with atherosclerosis, aortic valvular disease and left ventricular hypertrophy with rhythm and conduction defects. A 29-year-old woman presented with a partial lipodystrophy syndrome and a severe coronary atherosclerosis which required a triple coronary artery bypass grafting. She carried the novel heterozygous p.(Arg60Pro) LMNA variant inherited from her mother, affected with partial lipodystrophy and dilated cardiomyopathy. Different lipodystrophy-associated LMNA pathogenic variants could target cardiac vasculature and/or muscle, leading to complex overlapping phenotypes. Unifying pathophysiological hypotheses should be explored in several cell models including adipocytes, cardiomyocytes and vascular cells. Patients with LMNA-associated lipodystrophy should be systematically investigated with 24-h ECG monitoring, echocardiography and non-invasive coronary function testing.
Published: 2020

6. Erratum. Ten-Year Outcome of Islet Alone or Islet After Kidney Transplantation in Type 1 Diabetes: A Prospective Parallel-Arm Cohort Study. Diabetes Care 2019;42:2042-2049

Author: Eric Van Belle, François Machuron, Marc Hazzan, Marie-Christine Vantyghem, Christian Noel, Thomas Hubert, Robert Caiazzo, Stéphanie Espiard, Julie Kerr-Conte, Arnaud Jannin, Violeta Raverdy, Pascal Pigny, François Pattou, Nathalie Delalleau, Valery Gmyr, Kristell Le Mapihan, Marie Frimat, Mikael Chetboun, Université de Lille, LillOA, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille, Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - USR 3290 (MSAP), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Inserm, CHU Lille, Recherche translationnelle sur le diabète (RTD) - U1190, Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Récepteurs nucléaires, Maladies Cardiovasculaires et Diabète (EGID) - U1011, Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE], Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD], Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 [MSAP], Lille Inflammation Research International Center - U 995 [LIRIC], and Recherche translationnelle sur le diabète - U 1190 [RTD]
Subjects: Advanced and Specialized Nursing, Type 1 diabetes, medicine.medical_specialty, geography, geography.geographical_feature_category, business.industry, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], MEDLINE, 030209 endocrinology & metabolism, medicine.disease, Islet, 3. Good health, Islet after kidney, Transplantation, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, 030212 general & internal medicine, business, Cohort study
Abstract: The names of the working groups that collaborated in the study reported in this article were inadvertently omitted from the byline. The corrected byline should … 2019;42
Published: 2020

7. Diagnostic Challenge in PLIN1-Associated Familial Partial Lipodystrophy

Author: Marie-Christine Vantyghem, Martine Auclair, Olivier Lascols, David B. Savage, Camille Vatier, Elise Bismuth, Isabelle Jéru, Sara Barraud, Pascale Cervera, Corinne Vigouroux, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Sorbonne Paris Cité (USPC), Université Pierre et Marie Curie - Paris 6 (UPMC), Pathologie de l'Adipocyte et des Cellules Hepatiques, University of Cambridge [UK] (CAM), and Barraud, Sara
Subjects: 0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, DNA Mutational Analysis, Case Report, Bioinformatics, Biochemistry, 0302 clinical medicine, Endocrinology, Hyperinsulinemia, Frameshift Mutation, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, education.field_of_study, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Polycystic ovary, 3. Good health, Lipodystrophy, Familial Partial, Pedigree, Phenotype, Molecular Diagnostic Techniques, Female, Lipodystrophy, Adult, medicine.medical_specialty, Perilipin-1, Population, 030209 endocrinology & metabolism, Frameshift mutation, Diagnosis, Differential, 03 medical and health sciences, Young Adult, Insulin resistance, Diabetes mellitus, Internal medicine, medicine, Humans, Family, education, Aged, business.industry, Biochemistry (medical), Sequence Analysis, DNA, medicine.disease, Familial partial lipodystrophy, 030104 developmental biology, Insulin Resistance, business
Abstract: Context Heterozygous frameshift variants in PLIN1 encoding perilipin-1, a key protein for lipid droplet formation and triglyceride metabolism, have been implicated in familial partial lipodystrophy type 4 (FPLD4), a rare entity with only six families reported worldwide. The pathogenicity of other PLIN1 null variants identified in patients with diabetes and/or hyperinsulinemia was recently questioned because of the absence of lipodystrophy in these individuals and the elevated frequency of PLIN1 null variants in the general population. Objectives To reevaluate the pathogenicity of PLIN1 frameshift variants owing to new data obtained in the largest series of patients with FPLD4. Methods We performed histological and molecular studies for patients referred to our French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity for lipodystrophy and/or insulin resistance and carrying PLIN1 frameshift variants. Results We identified two heterozygous PLIN1 frameshift variants segregating with the phenotype in nine patients from four unrelated families. The FPLD4 stereotypical signs included postpubertal partial lipoatrophy of variable severity, muscular hypertrophy, acromegaloid features, polycystic ovary syndrome and/or hirsutism, metabolic complications (e.g., hypertriglyceridemia, liver steatosis, insulin resistance, diabetes), and disorganized subcutaneous fat lobules with fibrosis and macrophage infiltration. Conclusions These data suggest that some FPLD4-associated PLIN1 variants are deleterious. Thus, the evidence for the pathogenicity of each variant ought to be carefully considered before genetic counseling, especially given the importance of an early diagnosis for optimal disease management. Thus, we recommend detailed familial investigation, adipose tissue-focused examination, and follow-up of metabolic evolution.
Published: 2019

8. LMNA-linked lipodystrophy : new insight on cardiovascular phenotypes

Author: Corinne Vigouroux, Rabah Ben Yaou, Isabelle Jeru, Caroline Stalens, Olivier Lascols, Gisèle Bonne, Marie-Christine Vantyghem, Corinne Vatier, Karim Wahbi, The French Opale Observatory Investigators, 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), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Association française contre les myopathies (AFM-Téléthon), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [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)-CHU Pitié-Salpêtrière [AP-HP], Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: [SDV.GEN]Life Sciences [q-bio]/Genetics, Laminopathies, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism
Abstract: Communication orale; International audience
Published: 2019

9. Non-islet-cell tumour hypoglycaemia (NICTH): About a series of 6 cases

Author: Stéphanie Espiard, Kanza Benomar, Marie-Christine Vantyghem, Henri Porte, Christine Do Cao, Nicolas Penel, Bénédicte Mycinski, Arnaud Jannin, Michèle d’Herbomez, Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Adult, Blood Glucose, Male, medicine.medical_specialty, Solitary fibrous tumor, Fibrosarcoma, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Fibroma, Neuroendocrine tumors, Hypoglycemia, Gastroenterology, Asymptomatic, Hospitals, University, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin-Like Growth Factor II, Interquartile range, Internal medicine, Meningeal Neoplasms, medicine, Humans, Magnesium, Retroperitoneal Neoplasms, Insulin-Like Growth Factor I, Aged, Hemangiopericytoma, Human Growth Hormone, business.industry, General Medicine, Prognosis, medicine.disease, Hypokalemia, 3. Good health, Solitary Fibrous Tumor, Pleural, Pleural Solitary Fibrous Tumor, Neuroendocrine Tumors, 030220 oncology & carcinogenesis, Potassium, Female, medicine.symptom, business
Abstract: The purpose of this study was to analyse the characteristics of 6 patients managed in a university hospital between 1996 and 2016 for non-islet cell tumor hypoglycemia (NICTH), a form of hypoglycaemia due to the paraneoplastic secretion of IGF-2 or its related substances. RESULTS: Three of these 6 patients (50%), aged over 69 years, including 2 with acromegaloid phenotype, presented with a pleural solitary fibrous tumor (SFT), with median diameter 20 cm (interquartile range, 12.5-20.5) with a low median SUV (3.3 g/mL (QR, 2-7.5)) on 18F-FDG PET. The other 3 patients presented respectively neuroendocrine carcinoma (NEC) of the palate (70-year-old woman), retroperitoneal myxofibrosarcoma (66-year-old man) and meningeal hemangiopericytoma (36-year-old woman). All 3 were inoperable and did not respond to any therapy other than glucose solution. Corticosteroid therapy was effective in the 3 SFTs and the NEC. One of the SFTs recurred 10 years later with asymptomatic hypoglycemia, which resolved after reintervention. Median (IQR) blood glucose levels of the 6 patients was 0.4g/L (QR, 0.31-0.41), with hypoinsulinemia at 0.7mIU/L (QR 0.7-2.0), undetectable GH, low IGF-1, normal IGF-2 level in 5/6 cases, a high IGF-2:IGF-1 ratio at 26.9 (QR, 20.8-37.8), hypokalemia and hypomagnesemia. CONCLUSION: NICTH is a rare syndrome, which should be considered in the presence of hypoinsulinemic hypoglycemia with low GH and IGF-1, and a IGF-2:IGF-1 ratio>10. Corticosteroid therapy was effective in elderly subjects, particularly with solitary fibrous tumor, which was generally operable. Hemangiopericytoma and myxofibrosarcoma had poor prognosis in younger patients.
Published: 2019

10. Monogenic forms of lipodystrophic syndromes - diagnosis, detection, and practical management considerations from clinical cases

Author: Corinne Vigouroux, Marie-Christine Vantyghem, Camille Vatier, Jean-Claude Carel, Sophie Christin-Maitre, Bruno Fève, Isabelle Jéru, Jacques Beltrand, Olivier Lascols, Caroline Storey, Elise Bismuth, Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], CHU Saint-Antoine [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), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'endocrinologie, gynécologie et diabétologie pédiatriques [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'endocrinologie, diabétologie et nutrition, Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF)-Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13), Gestionnaire, Hal Sorbonne Université, 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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [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)-CHU Pitié-Salpêtrière [AP-HP], Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Cité (USPC)-Hôpital Jean Verdier [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre de Recherche en Nutrition Humaine - Ile de France (CRNH - IDF)
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Lipodystrophy, Familial partial lipodystrophy, Berardinelli-Seip congenital lipodystrophy, Early detection, Consanguinity, 030204 cardiovascular system & hematology, Metreleptin, Congenital generalized lipodystrophy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, GTP-Binding Protein gamma Subunits, medicine, Humans, 030212 general & internal medicine, Aged, Metabolic Syndrome, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, business.industry, Infant, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Fatty Liver, chemistry, Mutation, Berardinelli-Seip Congenital Lipodystrophy, Female, business, Acyltransferases
Abstract: International audience; BACKGROUND: Lipodystrophic syndromes are rare diseases of genetic or acquired origin characterized by partial or generalized lack of body fat. Early detection and diagnosis are crucial to prevent and manage associated metabolic dysfunctions, i.e. insulin resistance, dyslipidemia, fatty liver, and diabetes, and to provide appropriate genetic counseling. By means of several representative case studies, this article illustrates the diagnostic and management challenges of lipodystrophic syndromes.REVIEW: Berardinelli-Seip congenital lipodystrophy (BSCL) is typically diagnosed at birth, or soon thereafter, with generalized lipoatrophy and hepatomegaly secondary to hepatic steatosis. Physicians must also consider this diagnosis in adults with atypical non-autoimmune diabetes, hypertriglyceridemia, and a lean and muscular phenotype. The BSCL1 subtype due to mutations in the AGPAT2 gene can have an unusual presentation, especially in neonates and infants. Particular attention should be paid to infants presenting failure to thrive who also have hepatomegaly and metabolic derangements. The BSCL2 sub-type due to mutations in the BSCL gene tends to be more severe than BSCL1, and is characterized by greater fat loss, mild intellectual disability, earlier onset of diabetes, and higher incidence of premature death. Effective management from an earlier age may moderate the natural disease course. Partial lipodystrophies may easily be confused with common central obesity and/or metabolic syndrome. In patients with unexplained pancreatitis and hypertriglyceridemia, lipodystrophies such as familial partial lipodystrophy type 2 (FPLD2; Dunnigan type, due to LMNA mutations) should be considered. Oral combined contraceptives, which can reveal the disease by inducing severe hypertriglyceridemia, are contraindicated. Endogenous estrogens may also lead to "unmasking" of the FPLD2 phenotype, which often appears at puberty, and is more severe in females than males.CONCLUSIONS: Diet and exercise, adapted to age and potential comorbidities, are essential prerequisites for therapeutic management of lipodystrophic syndromes. Metreleptin therapy can be useful to manage lipodystrophy-related metabolic complications
Published: 2019

11. Cardiometabolic assessment of lamin A/C gene mutation carriers: A phenotype-genotype correlation

Author: F. Brigadeau, Gisèle Bonne, Sandro Ninni, R. Ben Yaou, P. Degroote, D. Klug, A. Ben Hamou, Arnaud Jannin, J.M. Laurent, M. Kwapich, C. Kouakam, Marie-Christine Vantyghem, Linda Humbert, P. Richard, V. Tiffreau, Corinne Vigouroux, Céline Tard, Nicolas Lamblin, S. Espiard, Dominique Lacroix, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 (URePSSS), Université d'Artois (UA)-Université de Lille-Université du Littoral Côte d'Opale (ULCO), Troubles cognitifs dégénératifs et vasculaires - U 1171 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Recherche translationnelle sur le diabète - U 1190 (RTD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Lille, Institut Coeur Poumon [CHU Lille], Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Troubles cognitifs dégénératifs et vasculaires - U 1171 - EA 1046 (TCDV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), 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), Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), 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 Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508 (EGID), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), European Genomic Institute for Diabetes - FR 3508 (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), CCSD, Accord Elsevier, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, and Centre de Recherche en Myologie
Subjects: Male, Lipodystrophy, Laminopathy, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, 030204 cardiovascular system & hematology, Gene mutation, Gastroenterology, Coronary artery disease, LMNA, 0302 clinical medicine, Endocrinology, Gene Frequency, Rhythm disorders, Genotype, Left atrial enlargement, Longitudinal Studies, Leptin, General Medicine, Middle Aged, Lamin Type A, Lipodystrophy, Familial Partial, 3. Good health, [SDV] Life Sciences [q-bio], Cardiovascular Diseases, Female, LMNAgene, Adult, Heterozygote, medicine.medical_specialty, 030209 endocrinology & metabolism, Sudden death, Young Adult, 03 medical and health sciences, Metabolic Diseases, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, Genetic Association Studies, Retrospective Studies, business.industry, medicine.disease, Case-Control Studies, Mutation, business
Abstract: International audience; Aims: Mutations of the LMNA gene encoding lamin A/C induce heterogeneous phenotypes ranging from cardiopathies and myopathies to lipodystrophies. The aim of this study was to compare cardiometabolic complications in patients with heterozygous LMNA mutations at the 482nd codon, the 'hotspot' for partial lipodystrophy, with carriers of other, non-R482 LMNA mutations.Methods and results: This study included 29 patients with R482 LMNA mutations, 29 carriers of non-R482 LMNA mutation and 19 control subjects. Cardiac and metabolic phenotypes were compared between groups. A family history of either cardiac implantable electronic devices (CIEDs; P < 0.001) or sudden death (P < 0.01) was more frequent in non-R482 than R482 carriers. The non-R482 carriers also had more abnormalities on electrocardiography and received CIEDs more often than R482 carriers (P < 0.001). On cardiac ultrasound, non-R482 patients had greater frequencies of left atrial enlargement (P < 0.05) and lower left ventricular ejection fractions (P < 0.01) than R482 carriers. In contrast, R482 carriers had lower BMI (P < 0.05), leptin (P < 0.01) and fat mass (P < 0.001), but higher intra-/total abdominal fat-mass ratios (P < 0.001) and prevalences of diabetes (P < 0.01) and hypertriglyceridaemia (P < 0.05) than non-R482 carriers, with a trend towards more coronary artery disease. However, non-R482 carriers had higher intra-/total abdominal fat-mass ratios (P < 0.02) and prevalences of diabetes (P < 0.001) and hypertriglyceridaemia (P < 0.05) than the controls.Conclusion: Non-R482 carriers present more frequently with arrhythmias than R482 carriers, who twice as often have diabetes, suggesting that follow-up for laminopathies could be adjusted for genotype. Non-R482 mutations require ultra-specialized cardiac follow-up, and coronary artery disease should not be overlooked. Although overlapping phenotypes are found, LMNA mutations essentially lead to tissue-specific diseases, favouring genotype-specific pathophysiological mechanisms.
Published: 2018

12. Indications for islet or pancreatic transplantation: Statement of the TREPID working group on behalf of the Société francophone du diabète (SFD), Société francaise d’endocrinologie (SFE), Société francophone de transplantation (SFT) and Société française de néphrologie – dialyse – transplantation (SFNDT)

Author: Nassim Kamar, Thierry Berney, Georges Karam, Gabriella Pittau, Oriana Ciacio, F. Buron, Julien Branchereau, M. Chetboun, Karine Moreau, Bogdan Catargi, Pierre Cattan, Sophie Reffet, Kristell Le Mapihan, Michelle Elias, Jean-Pierre Duffas, Marie-Noelle Peraldi, Sandrine Lablanche, Paolo Malvezzi, Jean-Emmanuel Serre, Gianluca Donatini, Laurence Kessler, Emmanuel Cuellar, Marie Frimat, Sophie Ohlmann, Chailloux Lucy, Xavier Tillou, Jean-Pierre Riveline, Fabrizio Panaro, Marie-Christine Vantyghem, Antoine Durrbach, Tiphaine Vidal-Trecan, François Pattou, Pierre-Yves Benhamou, Mathieu Armanet, Anne Wojtusciszyn, Hélène Hanaire, Sophie Caillard, Vincent Melki, Antonio Sacunha, Emmanuel Morelon, L. Esposito, Choukroun Gabriel, Anne Lejay, Francois Gaudez, Gilles Blancho, Gaëtan Prévost, Lionel Badet, Valérie Garrigue, Rachel Tetaz, Olivier Thaunat, Axel Andres, Fabrice Muscari, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lapeyronie [Montpellier] (CHU), Centre hospitalier universitaire de Nantes (CHU Nantes), Immunotherapy in Transplantation And Autoimmunity (Team 3 - 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), Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse]-PRES Université de Toulouse, Service d'urologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université Lille Nord de France (COMUE), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), CHU Strasbourg, Geneva University Hospital (HUG), Université Lille Nord (France), Laboratory of Fundamental and Applied Bioenergetics = Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Centre Hospitalier Universitaire [Grenoble] (CHU)
Subjects: Pediatrics, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Islets of Langerhans Transplantation, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Pancreas transplantation, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Diabetes mellitus, Internal Medicine, Humans, Medicine, Kidney transplantation, ComputingMilieux_MISCELLANEOUS, Type 1 diabetes, business.industry, Immunosuppression, General Medicine, medicine.disease, 3. Good health, Transplantation, Diabetes Mellitus, Type 1, Treatment Outcome, Pancreatic islet transplantation, Pancreas Transplantation, business, Allotransplantation
Abstract: While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.
Published: 2018

13. One-year metreleptin therapy decreases PCSK9 serum levels in diabetic patients with monogenic lipodystrophy syndromes

Author: A. Daguenel, Edith Bigot, Corinne Vigouroux, Xavier Prieur, Marie-Christine Vantyghem, Béatrice Guyomarch, Camille Vatier, L. Arnaud, Bertrand Cariou, J.F. Gautier, C. Le May, Matthieu Pichelin, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de diabétologie et d'endocrinologie [CHU Lariboisière], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Belgian Institute for Space Aeronomy / Institut d'Aéronomie Spatiale de Belgique (BIRA-IASB), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), 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)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Service d'Endocrinologie, Diabétologie et d'Endocrinologie de la Reproduction [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Lariboisière, 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) (APHP)-CHU Saint-Antoine [APHP], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP], Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie, diabétologie et endocrinologie de la reproduction [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: 0301 basic medicine, Adult, Leptin, Male, medicine.medical_specialty, Pediatrics, Adolescent, Lipodystrophy, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Cohort Studies, 03 medical and health sciences, Metreleptin, chemistry.chemical_compound, Young Adult, Endocrinology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Hypoglycemic Agents, ComputingMilieux_MISCELLANEOUS, Aged, Glycated Hemoglobin, business.industry, PCSK9, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, 030104 developmental biology, chemistry, Diabetes Mellitus, Type 2, Female, Proprotein Convertase 9, business, Biomarkers
Abstract: Diabetes & Metabolism - In Press.Proof corrected by the author Available online since mercredi 28 septembre 2016
Published: 2017

14. Evaluation of the occurrence of the manifestations of Carney complex in a french cohort of 70 patients during a three years standardized follow-up

Author: Herve Lefebvre, Catherine Cardot-Bauters, Marie-Christine Vantyghem, Francoise Archambeaud-Mouveroux, Olivier Chabre, Marie-Laure Nunes, Muriel Houang, Gérald Raverot, Jérôme Bertherat, Françoise Brucker-Davis, Stéphanie Espiard, Anne Lienhardt, Antoine Tabarin, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d’endocrinologie, diabétologie et maladies métaboliques [CHRU LIlle], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), Département d'endocrinologie - Bordeaux 2, Université Bordeaux Segalen - Bordeaux 2, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU), Service de Pédiatrie médicale - Spécialités médicales [CHU Limoges], CHU Limoges, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'Endocrinologie, Diabète et Maladies Métaboliques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service d'endocrinologie-diabétologie-nutrition [CHU Grenoble-Alpes], Centre Hospitalier Universitaire Grenoble Alpes (CHU Grenoble Alpes), Service d'Endocrinologie (BORDEAUX - Endocrino), CHU Bordeaux [Bordeaux], CHU Cochin [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Pediatrics, medicine.medical_specialty, business.industry, Cohort, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, business, Carney complex, 3. Good health
Abstract: International audience; IntroductionThe Carney Complex is a multiple endocrine and non endocrine neoplasia mostly due to PRKAR1A mutations. Spectrum of manifestations and genotypephenotype correlations have been previously described by retrospective studies. A prospective study evaluating the occurrence of the different manifestations was needed to precise the optimum follow-up.MethodsMulti-center national prospective study (Clinical Trials NCT00668291) including 70 patients mutated or wild-type for PRKAR1A followed prospectively during 3years with screening of the different manifestations by annual clinical, biological and radiological evaluation.ResultsThe cohort was compound of 50 females and 20 males with a mean age at 35.4years C/K16.7. Prevalence of cardiac myxomas at the end of the follow-up was 22.9% with newly diagnosis during the study period for 3 patients. Fortyfour% of patients with myxomas had related stroke attack and 56% had recurrences. Median delay between recurrences was 3.8years (minimummaximum: 0.8–24). Primary pigmented adrenal nodular disease was diagnosed in 57.1%. Skin manifestations, abnormal somatotroph hormonal tests and thyroid tumors were observed respectively in 58.6, 21.4 and 12.9%. Four% had melanotic shwannomas confirmed by histology. Spinal magnetic resonance imagery revealed lesions for 8.6%. Characteristic multiples calcified tumors on testicular ultrasonography were present in 35% of male patients. Ten% of female patients had surgery for breast myxoma or adenofibroma. Forty% had lesions classified ACR2-3 at mammography. Interestingly, four patients (8%) had breast adenocarcinomas (11.1% of female older than 30years). Eighty-three% of patients had PRKAR1A mutations. Patients carrying the mutation c.709-7del6 (34% of the cohort) had no manifestation or phenotype restricted to adrenal, lentigines and abnormal somatotroph test.ConclusionThe penetrance of the disease is high after screening except for patient carrying the c.709-7del6 mutation. This study highlights the importance of an annual follow-up, with especially annual cardiac imaging for patients with history of cardiac myxomas and earlier and regular senologic evaluation.DOI: 10.1530/endoabs.49.GP120
Published: 2017

15. PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease

Author: Bruno Ragazzon, Isabelle Boutelet, Julien Wils, Marthe Rizk-Rabin, Estelle Louiset, Zakariae Bram, Marie-Christine Vantyghem, Rossella Libé, Sylvie Renouf, Constantine A. Stratakis, Eva Szarek, Céline Duparc, Dennis A. Carson, Antoine Martinez, Jacques Young, Hervé Lefebvre, Jérôme Bertherat, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), Neuroendocrinologie cellulaire et moléculaire, Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), CHU Cochin [AP-HP], Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie et Métabolisme, Section on Endocrinology and Genetics, National Institutes of Health (NIH)-National Institute of Child Health and Human Development, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), U693, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Sud (Paris 11), Recherche translationelle sur le diabète (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut Européen de Génomique du Diabète - EGID, Département d'Endocrinologie, Diabète et Maladies Métaboliques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU), Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), ANR-06-MRAR-0002,Complexe de Carney,Physiopathologie et Génétique de la dysplasie micronodulaire pigmentée des surrénales (PPNAD) et du complexe de Carney (CNC).(2006), and ANR-08-GENO-0007,Complexe de Carney,Physiopathologie et génétique de la dysplasie micronodulaire pigmentée des surrénales (PPNAD) et du complexe de Carney (CNC)(2008)
Subjects: 0301 basic medicine, Male, MESH: Signal Transduction, Receptor expression, [SDV]Life Sciences [q-bio], Tryptophan Hydroxylase, 0302 clinical medicine, MESH: Child, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Child, PRKAR1A, ComputingMilieux_MISCELLANEOUS, MESH: Middle Aged, TPH2, General Medicine, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, MESH: Young Adult, Child, Preschool, Female, Signal transduction, Signal Transduction, Research Article, Adrenal Cortex Diseases, Adult, medicine.medical_specialty, Serotonin, MESH: Receptors, Serotonin, MESH: Mutation, Adolescent, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Serotonergic, Cell Line, 03 medical and health sciences, Young Adult, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, MESH: Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, Protein kinase A, MESH: Adolescent, MESH: Humans, MESH: Adrenal Cortex Diseases, MESH: Child, Preschool, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Tryptophan hydroxylase, MESH: Male, MESH: Tryptophan Hydroxylase, MESH: Cell Line, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, Endocrinology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Receptors, Serotonin, Mutation, MESH: Serotonin, MESH: Female, Primary pigmented nodular adrenocortical disease
Abstract: International audience; Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent hypercortisolism. The disease is primarily caused by germline mutations of the protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene, which induces constitutive activation of PKA in adrenocortical cells. Hypercortisolism is thought to result from PKA hyperactivity, but PPNAD tissues exhibit features of neuroendocrine differentiation, which may lead to stimulation of steroidogenesis by abnormally expressed neurotransmitters. We hypothesized that serotonin (5-HT) may participate in the pathophysiology of PPNAD-associated hypercortisolism. We show that PPNAD tissues overexpress the 5-HT synthesizing enzyme tryptophan hydroxylase type 2 (Tph2) and the serotonin receptors types 4, 6, and 7, leading to formation of an illicit stimulatory serotonergic loop whose pharmacological inhibition in vitro decreases cortisol production. In the human PPNAD cell line CAR47, the PKA inhibitor H-89 decreases 5-HT4 and 5-HT7 receptor expression. Moreover, in the human adrenocortical cell line H295R, inhibition of PRKAR1A expression increases the expression of Tph2 and 5-HT4/6/7 receptors, an effect that is blocked by H-89. These findings show that the serotonergic process observed in PPNAD tissues results from PKA activation by PRKAR1A mutations. They also suggest that Tph inhibitors may represent efficient treatments of hypercortisolism in patients with PPNAD.
Published: 2016

16. LMNA mutations resulting in lipodystrophy and HIV protease inhibitors trigger vascular smooth muscle cell senescence and calcification: Role of ZMPSTE24 downregulation

Author: Christine Katlama, Franck Boccara, Martine Caron-Debarle, Marie-Christine Vantyghem, Jacqueline Capeau, Corinne Vigouroux, Martine Auclair, Pauline Afonso, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Cardiologie [CHU Saint-Antoine], CHU Saint-Antoine [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), Service d'Endocrinologie et Métabolisme, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [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), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Laboratoire commun de biologie et génétique moléculaires [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), HAL-UPMC, Gestionnaire, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and CHU Tenon [AP-HP]
Subjects: 0301 basic medicine, Senescence, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, Lipodystrophy, Osteogenic transdifferentiation, DNA Mutational Analysis, Cell, Down-Regulation, Inflammation, 030204 cardiovascular system & hematology, Biology, medicine.disease_cause, LMNA, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Prelamin A, Internal medicine, medicine, Vascular smooth muscle cells, Humans, Vascular Calcification, Cells, Cultured, Cellular Senescence, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, integumentary system, Reverse Transcriptase Polymerase Chain Reaction, ZMPSTE24, Transdifferentiation, Membrane Proteins, Metalloendopeptidases, nutritional and metabolic diseases, DNA, HIV Protease Inhibitors, Lamin Type A, medicine.disease, Atherosclerosis, 3. Good health, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Mutation, medicine.symptom, Cardiology and Cardiovascular Medicine, Oxidative stress, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Calcification
Abstract: International audience; BackgroundSome LMNA mutations responsible for lipodystrophies, and some HIV-protease inhibitors (PIs) induce accumulation of farnesylated prelamin A and premature senescence in some cell types. Patients with LMNA mutations or under PI-based therapy suffer from early atherosclerosis. The metalloprotease ZMPSTE24 is the key enzyme in prelamin A maturation.AimWe studied whether altered expression of ZMPSTE24 could contribute to vascular cell dysfunction in response to LMNA mutations or PI treatments.MethodsProtein expression of prelamin A and ZMPSTE24 were evaluated in patients' cells and in human cultured VSMCs. Oxidative stress, inflammation, senescence and transdifferentiation/calcification were evaluated in VSMCs.ResultsFibroblasts from LMNA-mutated lipodystrophic patients (mutations R482W, D47Y or R133L) and peripheral blood mononuclear cells from PI-treated-HIV-infected patients expressed increased prelamin A and decreased ZMPSTE24, which was also observed in VSMCs overexpressing mutant LMNA or treated with PIs. These alterations correlated with oxidative stress, inflammation, senescence and calcification (all p < 0.05). ZMPSTE24 silencing in native VSMCs recapitulated the mutant LMNA- and PI-induced accumulation of farnesylated prelamin A, oxidative stress, inflammation, senescence and calcification. A negative regulator of ZMPSTE24, miRNA-141-3p, was enhanced in LMNA-mutated or PI-treated VSMCs. The farnesylation inhibitors pravastatin and FTI-277, or the antioxidant N-acetyl cysteine, partly restored ZMPSTE24 expression, and concomitantly decreased oxidative stress, inflammation, senescence, and calcification of PI-treated VSCMs.ConclusionsZMPSTE24 downregulation is a major contributor in VSMC dysfunctions resulting from LMNA mutations or PI treatments that could translate in early atherosclerosis at the clinical level. These novel pathophysiological mechanisms could open new therapeutic perspectives for cardiovascular aging.
Published: 2016

17. Management of clinically non-functioning pituitary adenoma

Author: Chiara Villa, Francois Cotton, Guillaume Assié, Marie-Christine VANTYGHEM, Frederic Castinetti, Francoise Borson-Chazot, Anne Barlier, Service d'endocrinologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupement Hospitalier Lyon-Est (GHE), Hospices Civils de Lyon (HCL), 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), 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), Service Endocrinologie, diabétologie, maladies métaboliques et nutrition (LILLE - Endocrino), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'endocrinologie diabétologie et nutrition [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), 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), Service d'Endocrinologie (LILLE - Endocrino), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Anne-de-Bretagne
Subjects: Adenoma, Pituitary incidentaloma, medicine.medical_specialty, Consensus, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Context (language use), Disease, Pituitary neoplasm, Incidentalomes hypophysaires, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Acromegaly, medicine, Adénomes gonadotropes, Humans, Pituitary Neoplasms, Silent pituitary adenoma, Radiothérapie, Gynecology, business.industry, General surgery, Incidentaloma, Pituitary apoplexy, General Medicine, medicine.disease, Pituitary surgery, Apoplexie hypophysaire, 3. Good health, Radiation therapy, Gonadotroph adenoma, Non-functioning pituitary adenoma, Non-secreting pituitary adenoma, Chirurgie hypophysaire, Adénomes hypophysaires non sécrétants, business, Pituitary Apoplexy, 030217 neurology & neurosurgery, Adénomes hypophysaires non fonctionnels, Adénomes hypophysaires silencieux
Abstract: International audience; Clinically NFPA is currently the preferred term for designing all the pituitary adenomas which are not hormonally active (in other words, not associated with clinical syndromes such as amenorrhea-galactorrhea in the context of prolactinomas, acromegaly, Cushing's disease or hyperthyroidism secondary to TSH-secreting adenomas). They account for 15-30% of pituitary adenomas. Diagnosis is usually made either in the context of mass effect due to a macroadenoma or, increasingly, fortuitously during imaging performed for some unrelated purpose; the latter case is known as pituitary incidentaloma. Surgery is indisputably indicated in case of tumoral syndrome, but other aspects of NFPA (hormonal work-up, follow-up, and especially postoperative follow-up, management of remnant or recurrence, the special case of incidentaloma, or apoplexy) remain controversial. The French Endocrinology Society (SFE) therefore set up an expert working group of endocrinologists, neurosurgeons, ophthalmologists, neuroradiologists, pathologists and biologists to draw up guidelines, at the 2012 SFE Congress in Toulouse, France. The present article presents the guidelines suggested by this group of French-speaking experts
Published: 2015

18. 15q11.2 microdeletion (BP1–BP2) and developmental delay, behaviour issues, epilepsy and congenital heart disease: A series of 52 patients

Author: Marie-Christine Vantyghem, Delphine Fauvert, Bénédicte Duban, Florence Petit, Frenny Sheth, Roseline Caumes, Louis Vallée, Valérie Malan, Guillaume Jedraszak, Jean-Marie Cuisset, Odile Boute, Patricia Blanchet, Valérie Cormier-Daire, Matthieu Decamp, Marie Pigeyre, Marion Gérard, Joelle Roume, Sandrine Lanco-Dosen, Nathalie Lemeur, Pierre Sarda, Muriel Holder-Espinasse, Jacques Puechberty, Frédéric Bilan, Gilles Morin, Lucie Pinson, David Geneviève, Ghislaine Plessis, Bruno Delobel, Marie-Pierre Lemaitre, Sylvie Manouvrier-Hanu, Clémence Vanlerberghe, Brigitte Gilbert-Dussardier, Sonia Bouquillon, Joris Andrieux, Catherine Vincent-Delorme, Michèle Mathieu, Institut de Génétique Médicale [CHRU Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de génétique clinique (CHU Lille), Laboratoire Histologie Embryologie Cytogénétique [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Guy's Hospital [London], Hôpital Saint-Vincent de Paul, Service de Neuro-pédiatrie[Lille], Hôpital Claude Huriez [Lille], CHU Lille, CHR Sambre-Avesnois, Institut Lillois d'Ingénierie de la Santé (ILIS), Université de Lille, Droit et Santé-Université de Lille, Droit et Santé, Service de Génétique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Amiens-Picardie, Service Génétique Médicale [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de génétique clinique [Poitiers], CHI Poissy-Saint-Germain, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), CHU Rouen, Normandie Université (NU), Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Male, Pediatrics, Heart disease, Developmental Disabilities, Aneuploidy, 15q11.2 microdeletion, Cohort Studies, Epilepsy, 0302 clinical medicine, Copy-number variation, Child, Cation Transport Proteins, Genetics (clinical), In Situ Hybridization, Fluorescence, Genetics, 0303 health sciences, Comparative Genomic Hybridization, Mental Disorders, General Medicine, Middle Aged, Penetrance, 3. Good health, Phenotype, Child, Preschool, Cohort, Female, Chromosome Deletion, Microtubule-Associated Proteins, Adult, medicine.medical_specialty, Adolescent, DNA Copy Number Variations, Heart Diseases, NIPA2, NIPA1, Speech Disorders, CYFIP1, 03 medical and health sciences, Chromosome 15, Young Adult, BP1–BP2, Intellectual Disability, TUBGCP5, medicine, Humans, Generalized epilepsy, 030304 developmental biology, Adaptor Proteins, Signal Transducing, Congenital heart disease, Chromosome Aberrations, Chromosomes, Human, Pair 15, business.industry, Infant, Membrane Proteins, medicine.disease, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Attention Deficit Disorder with Hyperactivity, Child Development Disorders, Pervasive, business, 030217 neurology & neurosurgery
Abstract: International audience; Proximal region of chromosome 15 long arm is rich in duplicons that, define five breakpoints (BP) for 15q rearrangements. 15q11.2 microdeletion between BP1 and BP2 has been previously associated with developmental delay and atypical psychological patterns. This region contains four highly-conserved and non-imprinted genes: NIPA1, NIPA2, CYFIP1, TUBGCP5. Our goal was to investigate the phenotypes associated with this microdeletion in a cohort of 52 patients. This copy number variation (CNV) was prevalent in 0.8% patients presenting with developmental delay, psychological pattern issues and/or multiple congenital malformations. This was studied by array-CGH at six different French Genetic laboratories. We collected data from 52 unrelated patients (including 3 foetuses) after excluding patients with an associated genetic alteration (known CNV, aneuploidy or known monogenic disease). Out of 52 patients, mild or moderate developmental delay was observed in 68.3%, 85.4% had speech impairment and 63.4% had psychological issues such as Attention Deficit and Hyperactivity Disorder, Autistic Spectrum Disorder or Obsessive-Compulsive Disorder. Seizures were noted in 18.7% patients and associated congenital heart disease in 17.3%. Parents were analysed for abnormalities in the region in 65.4% families. Amongst these families, 'de novo' microdeletions were observed in 18.8% and 81.2% were inherited from one of the parents. Incomplete penetrance and variable expressivity were observed amongst the patients. Our results support the hypothesis that 15q11.2 (BP1-BP2) microdeletion is associated with developmental delay, abnormal behaviour, generalized epilepsy and congenital heart disease. The later feature has been rarely described. Incomplete penetrance and variability of expression demands further assessment and studies.
Published: 2015

19. Hormonal, Radiological, NP-59 Scintigraphy, and Pathological Correlations in Patients With Cushing's Syndrome Due to Primary Pigmented Nodular Adrenocortical Disease (PPNAD)

Author: Delphine Vezzosi, Sylvie Hiéronimus, Marie-Christine Vantyghem, Xavier Bertagna, Frédérique Tissier, Paul Legmann, Marie Laloi-Michelin, Marie Bienvenu, Florence Tenenbaum, G. Barrande, Hervé Lefebvre, Jérôme Bertherat, Carmen A. Carrasco, Laure Cazabat, Antoine Tabarin, DUPARC, Céline, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et cytologie pathologiques = Service de Pathologie [CHU Pitié-Salpêtrière] (ACP), CHU Pitié-Salpêtrière [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), Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pontificia Universidad Católica de Chile (UC), Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier Régional d'Orléans (CHRO), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Hôpital l'Archet, Centre Hospitalier Universitaire de Bordeaux (CHU de Bordeaux), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de pathologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Male, Pathology, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Thyroid Gland, Scintigraphy, Biochemistry, chemistry.chemical_compound, Cushing syndrome, Endocrinology, Adrenal Glands, Medicine, Child, Cushing Syndrome, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Adosterol, medicine.diagnostic_test, Adrenalectomy, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Female, Radiology, Iodine, Adult, medicine.medical_specialty, Adolescent, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, Context (language use), [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Young Adult, Internal medicine, Preoperative Care, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, Carney Complex, Radionuclide Imaging, Carney complex, Pathological, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, business.industry, Biochemistry (medical), medicine.disease, Hormones, chemistry, Mutation, Radiopharmaceuticals, business, Tomography, X-Ray Computed, Primary pigmented nodular adrenocortical disease
Abstract: International audience; Context: Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTHindependent Cushing’s syndrome that may occur in an isolated form or as part of Carney complex. The diagnosis of this disease can be difficult preoperatively because computed tomography (CT)scan can be normal or suggest unilateral adrenal lesion, which can impede the correct diagnosis ofbilateral adrenal disease.Objective: The aim of our study was to describe the results of preoperative imaging (adrenal [6-131I]iodomethyl-19-norcholesterol] [NP-59] cintigraphy and standard adrenal CT scan) and their correlations with clinical, pathological, and genetics investigations in patients with PPNAD.Patients and Methods: Seventeen patients with ACTH-independent syndrome due to PPNAD were investigated with a standard adrenal CT scan and NP-59 scintigraphy. Hormonal, pathological, and genetics data were analyzed.Results: Four males and 13 females (median age, 27 y) were included. PPNAD was isolated in 11 patients (with PRKAR1A mutation, n 7; and without PRKAR1A mutation, n 4) and was associated with extra-adrenal manifestations of Carney complex in six patients (with PRKAR1A mutation, n 4; and without PRKAR1A mutation, n 2). Standard adrenal CT scan revealed micronodules in 11 patients, macronodules in three patients, and was normal in three patients. All patients demonstrated bilateral adrenal radiocholesterol uptake. Adrenal uptake was asymmetrical in 10 of 17 patients (59%). Asymmetrical uptake correlated with the presence of macronodules at pathological analysis (P .03).Conclusion: Standard adrenal CT scan most often reveals micronodules but there is no specific CT imaging. NP-59 scintigraphy always shows a bilateral adrenal uptake confirming the bilateral nature of the disease, but asymmetrical scintigraphic uptake can be observed in patients withmacronodules.
Published: 2015

20. Lipodystrophy-Linked LMNA p.R482W Mutation Induces Clinical Early Atherosclerosis and In Vitro Endothelial Dysfunction

Author: Guillaume Bidault, Corinne Vigouroux, Véronique Béréziat, Pierre-Henri Ducluzeau, Kayathri Thiyagarajah, Marie Garcia, Jacqueline Capeau, Sylviane Moritz, Marie-Christine Vantyghem, Romain Morichon, Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHRU de Tours, Service de Médecine Interne Nutrition, 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), Sorbonne Université (SU), Cytométrie et Imagerie Saint-Antoine (CISA), Unité Mixte de Service d'Imagerie et de Cytométrie [CHU Saint-Antoine] (UMS LUMIC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Male, 030204 cardiovascular system & hematology, medicine.disease_cause, Antioxidants, LMNA, 0302 clinical medicine, Transduction, Genetic, Endothelial dysfunction, Age of Onset, Cellular Senescence, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, integumentary system, Nuclear Proteins, Middle Aged, Lamin Type A, 3. Good health, Lipodystrophy, Familial Partial, Endothelial stem cell, Phenotype, Female, Lipodystrophy, medicine.symptom, Cardiology and Cardiovascular Medicine, medicine.drug, Adult, medicine.medical_specialty, Heterozygote, Nuclear Envelope, Inflammation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Nitric Oxide, Transfection, 03 medical and health sciences, Internal medicine, medicine, Cell Adhesion, Humans, Genetic Predisposition to Disease, Protein Precursors, 030304 developmental biology, Prenylation, nutritional and metabolic diseases, Endothelial Cells, Fibroblasts, medicine.disease, Atherosclerosis, Coculture Techniques, Oxidative Stress, Endocrinology, HEK293 Cells, Mutation, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Protein Processing, Post-Translational, Oxidative stress, Pravastatin, Lamin, DNA Damage
Abstract: Objective— Some mutations in LMNA , encoding A-type lamins, are responsible for Dunnigan-type-familial partial lipodystrophy (FPLD2), with altered fat distribution and metabolism. The high prevalence of early and severe cardiovascular outcomes in these patients suggests that, in addition to metabolic risk factors, FPLD2-associated LMNA mutations could have a direct role on the vascular wall cells. Approach and Results— We analyzed the cardiovascular phenotype of 19 FPLD2 patients aged >30 years with LMNA p.R482 heterozygous substitutions, and the effects of p.R482W-prelamin-A overexpression in human coronary artery endothelial cells. In 68% of FPLD2 patients, early atherosclerosis was attested by clinical cardiovascular events, occurring before the age of 45 in most cases. In transduced endothelial cells, exogenous wild-type-prelamin-A was correctly processed and localized, whereas p.R482W-prelamin-A accumulated abnormally at the nuclear envelope. Patients’ fibroblasts also showed a predominant nuclear envelope distribution with a decreased rate of prelamin-A maturation. Only p.R482W-prelamin-A induced endothelial dysfunction, with decreased production of NO, increased endothelial adhesion of peripheral blood mononuclear cells, and cellular senescence. p.R482W-prelamin-A also induced oxidative stress, DNA damages, and inflammation. These alterations were prevented by treatment of endothelial cells with pravastatin, which inhibits prelamin-A farnesylation, or with antioxidants. In addition, pravastatin allowed the correct relocalization of p.R482W-prelamin-A within the endothelial cell nucleus. These data suggest that farnesylated p.R482W-prelamin-A accumulation at the nuclear envelope is a toxic event, leading to cellular oxidative stress and endothelial dysfunction. Conclusions— LMNA p.R482 mutations, responsible for FPLD2, exert a direct proatherogenic effect in endothelial cells, which could contribute to patients’ early atherosclerosis.
Published: 2013

21. Is thyroid cancer recurrence risk increased after transplantation?

Author: Emmanuel Morelon, Françoise Bonichon, Marc Klein, Georges Mourad, Antony Kelly, Christine Do Cao, Sophie Leboulleux, Françoise Borson-Chazot, Marie-Elisabeth Toubert, Delphine Drui, Luc Frimat, Laurence Leenhardt, Patricia Niccoli, Claire Pouteil-Noble, Isabelle Faugeron, Martin Schlumberger, Marie-Christine Vantyghem, Ingrid Allix, Hélène Tisset, Pascal Roy, Nassim Kamar, Claire Bournaud, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), 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)-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), and 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)
Subjects: Adult, Male, Risk, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Context (language use), Disease, Biochemistry, Cystic fibrosis, Organ transplantation, Disease-Free Survival, Recurrence risk, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Follicular phase, Adenocarcinoma, Follicular, medicine, Humans, 030212 general & internal medicine, Thyroid Neoplasms, Child, Thyroid cancer, Aged, business.industry, Incidence, Biochemistry (medical), Organ Transplantation, Middle Aged, medicine.disease, Carcinoma, Papillary, 3. Good health, Transplantation, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business
Abstract: An increased cancer mortality is reported in transplanted patients.This multicentric study aimed to investigate the rate of thyroid cancer recurrence after transplantation.Sixty-eight patients (35 male/33 female) with a history of both thyroid cancer and organ transplantation were recruited via two nationwide French networks. Histological analysis identified 58 papillary (88%), 5 follicular (7.5%), and 3 poorly differentiated cancer cases (4.5 %). Thirty-one patients (52%) presented high recurrence risk tumors. In the 36 patients with thyroid cancer diagnosed after transplantation, the 5-year disease-free survival (DFS) was 74.7% (SE: 7.3%). One patient died after progression of a poorly differentiated cancer. Persistent disease was observed in six high-risk patients. One of them underwent a second transplantation and disease remained stable after 5 years of follow-up. Thyroid cancer had been diagnosed before transplantation in 32 patients. One patient with cystic fibrosis and thyroid lung metastases at the time of lung transplantation underwent a 4-year remission. For the 31 patients in remission at the time of transplantation, the 5-year DFS was 93.1% (SE: 4.8%). Two patients with local recurrence presented subsequent remission. For the entire study population, the 5-year and 9-year DFS were 81.9% (SE: 5.5%) and 75.6% (SE: 7.9%), respectively. Recurrence or persistent disease occurred in patients with high-risk tumors.The prognosis of thyroid cancer does not seem to be altered by transplantation. This suggests that a history of thyroid cancer should not be considered a contraindication.
Published: 2013

22. Spectrum of mutations in Gitelman syndrome

Author: Annabelle Venisse, Diana Kahila, Claire Rigothier, Bernard Grisart, Bruno Moulin, Marie-Christine Vantyghem, Ivan Tack, Anne-Paule Gimenez-Roqueplo, Franck Bridoux, Jean-Philippe Haymann, Olivier Devuyst, Hubert Nivet, Rosa Vargas-Poussou, Laurence Dubourg, Eva Riveira-Munoz, Anne Blanchard, Karin Dahan, Michel Godin, Pascal Houillier, Huguette Debaix, Bertrand Dussol, Robert J. Unwin, Xavier Jeunemaitre, Service de néphrologie - hémodialyse et transplantation rénale, Université de Poitiers-Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), Contrôle de la Réponse Immune B et des Lymphoproliférations ( CRIBL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Institute of Physiology, University of Zürich [Zürich] ( UZH ) -Zurich Center for Integrative Human Physiology, Klinik für Nephrologie, UniversitätsSpital, Division of Nephrology, UCL Medical School, Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Contrôle de la Réponse Immune B et des Lymphoproliférations (CRIBL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), University of Zürich [Zürich] (UZH)-Zurich Center for Integrative Human Physiology, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Universität Zürich [Zürich] = University of Zurich (UZH)-Zurich Center for Integrative Human Physiology, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, MESH : Molecular Sequence Data, MESH : Retrospective Studies, Receptors, Drug, Gene Dosage, 030232 urology & nephrology, MESH: Base Sequence, MESH : Child, Preschool, medicine.disease_cause, MESH: Gitelman Syndrome, MESH: Gene Dosage, MESH : Chloride Channels, 0302 clinical medicine, MESH : Child, MESH: Child, Missense mutation, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Solute Carrier Family 12, Member 3, MESH : Female, MESH : Gene Dosage, Child, Gene Rearrangement, Genetics, 0303 health sciences, Mutation, MESH: Middle Aged, Symporters, MESH: Genetic Testing, MESH: Genetic Predisposition to Disease, General Medicine, Middle Aged, MESH : Adult, 3. Good health, Nephrology, MESH: Young Adult, Child, Preschool, MESH : Symporters, MESH: Solute Carrier Family 12, Member 3, MESH : Gitelman Syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Mutation, MESH : Sensitivity and Specificity, Gitelman Syndrome, Adult, MESH: Symporters, MESH: Mutation, Adolescent, MESH: Gene Rearrangement, MESH : Male, Molecular Sequence Data, Non-allelic homologous recombination, MESH : Young Adult, MESH : Solute Carrier Family 12, Member 3, Biology, Sensitivity and Specificity, Gene dosage, Young Adult, 03 medical and health sciences, Chloride Channels, MESH: Receptors, Drug, MESH : Adolescent, MESH : Genetic Testing, medicine, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, Genetic Testing, Multiplex ligation-dependent probe amplification, Allele, Alleles, Retrospective Studies, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, MESH : Receptors, Drug, MESH: Alleles, MESH: Child, Preschool, MESH: Chloride Channels, MESH : Humans, MESH: Adult, MESH: Retrospective Studies, Gene rearrangement, MESH : Gene Rearrangement, Gitelman syndrome, medicine.disease, MESH: Male, MESH: Sensitivity and Specificity, Basic Research, MESH : Genetic Predisposition to Disease, MESH : Base Sequence, MESH : Alleles, MESH: Female
Abstract: International audience; Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.
Published: 2011

23. Viral Protein VP4 Is a Target of Human Antibodies Enhancing Coxsackievirus B4- and B3-Induced Synthesis of Alpha Interferon

Author: Pierre-Emmanuel Lobert, Didier Hober, Wassim Chehadeh, Jacques Weill, Pascal Pigny, Anne Goffard, Bernadette Lucas, Pierre Sauter, Gunnar V. Alm, Marie-Christine Vantyghem, Service d'endocrinologie pédiatrique [CHU Lille], Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie et Métabolisme, Department of Medical Sciences, Mucines Epitheliales : du Gene a la Fonction, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Pathogenèse virale du diabète de type 1 - ULR 3610 (Laboratoire de Virologie), and Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Adult, Viral protein, viruses, [SDV]Life Sciences [q-bio], Immunology, Alpha interferon, Cross Reactions, Biology, Coxsackievirus, H antigen, Antibodies, Viral, medicine.disease_cause, Microbiology, Peripheral blood mononuclear cell, 03 medical and health sciences, Reference Values, Virology, medicine, Humans, Child, Interferon alfa, 030304 developmental biology, 0303 health sciences, 030306 microbiology, Interferon-alpha, virus diseases, biology.organism_classification, Molecular biology, Enterovirus B, Human, 3. Good health, Titer, Diabetes Mellitus, Type 1, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Insect Science, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Leukocytes, Mononuclear, biology.protein, Pathogenesis and Immunity, Capsid Proteins, Antibody, medicine.drug
Abstract: Coxsackievirus B4 (CVB4)-induced production of alpha interferon (IFN-α) by peripheral blood mononuclear cells (PBMC) is enhanced in vitro by nonneutralizing anti-CVB4 antibodies from healthy subjects and, to a higher extent, from patients with insulin-dependent diabetes mellitus. In this study, we focused on identification of the viral target of these antibodies in CVB systems. High levels of IFN-α were obtained in supernatants of PBMC incubated with CVB4E2 or CVB3 and plasma from healthy subjects and, to a higher extent, from patients. The VP4 capsid proteins dissociated by heating at 56°C from CVB4E2 (VP4CVB4) and CVB3 (VP4CVB3) but not H antigen preincubated with plasma from healthy subjects or patients inhibited the plasma-dependent enhancement of CVB4E2- and CVB3-induced IFN-α synthesis. There was no cross-reaction between VP4CVB4and VP4CVB3in the inhibiting effect. IFN-α levels in culture supernatants showed dose-dependent correlation with anti-VP4 antibodies eluted from plasma specimens using VP4-coated plates. There were higher index values for anti-VP4 antibodies detected by enzyme-linked immunosorbent assay (ELISA) and higher proportions of positive detection in 40 patients than in 40 healthy subjects (80% versus 15% for anti-VP4CVB4). There was no relationship between the levels of anti-CVB neutralizing antibodies and the detection of anti-VP4 antibodies by ELISA. The CVB plasma-induced IFN-α levels obtained in PBMC cultures in the anti-VP4 antibody-positive groups were significantly higher than those obtained in the anti-VP4 antibody-negative groups regardless of the titers of anti-CVB neutralizing antibodies. These results show that VP4 is the target of antibodies involved in the plasma-dependent enhancement of CVB4E2- and CVB3-induced IFN-α synthesis by PBMC.
Published: 2005

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23 results on '"Marie-Christine Vantyghem"'

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23. Viral Protein VP4 Is a Target of Human Antibodies Enhancing Coxsackievirus B4- and B3-Induced Synthesis of Alpha Interferon

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