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1. Hematological malignancies in giant cell arteritis: a french population-based study

Author: Bernard Bonnotte, Georges Tarris, André Ramon, Maxime Samson, Morgane Mounier, Sylvain Audia, Marc Maynadié, Hélène Greigert, Louis Arnould, Catherine Creuzot-Garcher, Laurent Martin, Tibor Ponnelle, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Registre des hémopathies malignes de Côte d'Or, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie (CHU de Dijon), Cypath [Dijon], Cypath : siège social [Villeurbanne], Service d'hématologie biologique (CHU de Dijon), Julien, Sabine, and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Myeloid, Population, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, immune system diseases, Internal medicine, Epidemiology, medicine, Humans, Pharmacology (medical), cardiovascular diseases, hematological malignancies, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, education, skin and connective tissue diseases, Retrospective Studies, 030203 arthritis & rheumatology, education.field_of_study, business.industry, giant cell arteritis, Incidence, Incidence (epidemiology), Middle Aged, medicine.disease, 3. Good health, Population based study, Giant cell arteritis, 030104 developmental biology, medicine.anatomical_structure, Increased risk, [SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs, population-based study, Hematologic Neoplasms, cardiovascular system, Female, France, business
Abstract: Objectives An increased risk of haematological malignancies (HM) has been reported in GCA patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA. Methods All patients with GCA and HM living in Côte d’Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d’Or) and those having a positive temporal artery biopsy between 1 January 2001 and 31 December 2018. Results Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged >50 y, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients [standardized incidence ratios (SIR) = 2.71 and 5.16, respectively], with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of SIR depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56). Conclusions Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA.
Published: 2021

2. Mucosal-associated invariant T cells in giant cell arteritis

Author: Philippe Saas, Sylvain Audia, Claire Gerard, Bernard Bonnotte, Hélène Greigert, Claudie Cladière, T. Ghesquiere, Pierre-Henry Gabrielle, André Ramon, Maxime Samson, Coraline Genet, François Maurier, Georges Tarris, Catherine Creuzot-Garcher, Valérie Quipourt, Paul Ornetti, Hervé Devilliers, Marion Ciudad, Laurent Martin, Agnès Soudry-Faure, Marine Thébault, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Hospital Belle Isle, Service de Rhumatologie (CHU de Dijon), Plateforme d’Investigation Technologique [Centre d’Investigation Clinique 1432 module Plurithématique - Dijon] (PIT), Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] (CAPS), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre d'Investigation Clinique 1432 (Dijon) - Module Plurithématique : Périnatalité Cancérologie Handicap et Ophtalmologie (CIC-P803), Université de Bourgogne (UB)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Ophtalmologie (CHU de Dijon), Délégation à la recherche clinique et à l'innovation [CHU Dijon] (DRCI), Centre d'Investigation Clinique de Besançon (Inserm CIC 1431), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])
Subjects: Male, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Proliferation index, CD3, Biopsy, Immunology, Primary Cell Culture, Stimulation, Mucosal associated invariant T cell, Mucosal-Associated Invariant T Cells, Flow cytometry, Pathogenesis, Tissue Culture Techniques, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, medicine, Immunology and Allergy, Humans, Prospective Studies, Cells, Cultured, 030304 developmental biology, Aged, Cell Proliferation, 030203 arthritis & rheumatology, 0303 health sciences, medicine.diagnostic_test, biology, business.industry, giant cell arteritis, Interleukin-18, invariant t-cells, CD28, Middle Aged, medicine.disease, Interleukin-12, Healthy Volunteers, Temporal Arteries, Giant cell arteritis, mucosal associated invariant T, Case-Control Studies, biology.protein, Female, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Signal Transduction
Abstract: International audience; This study aimed to assess the implication of mucosal-associated invariant T (MAIT) cells in GCA. Blood samples were obtained from 34 GCA patients (before and after 3 months of treatment with glucocorticoids (GC) alone) and compared with 20 controls aged >50 years. MAIT cells, defined by a CD3(+)CD4(-)TCRγδ(-)TCRVα7.2(+)CD161(+) phenotype, were analyzed by flow cytometry. After sorting, we assessed the ability of MAIT cells to proliferate and produce cytokines after stimulation with anti CD3/CD28 microbeads or IL-12 and IL-18. MAIT were stained in temporal artery biopsies (TAB) by confocal microscopy. MAIT cells were found in the arterial wall of positive TABs but was absent in negative TAB. MAIT frequency among total αβ-T cells was similar in the blood of patients and controls (0.52 vs. 0.57%; P = 0.43) and not modified after GC treatment (P = 0.82). Expression of IFN-γ was increased in MAIT cells from GCA patients compared to controls (44.49 vs. 32.9%; P = 0.029), and not modified after 3 months of GC therapy (P = 0.82). When they were stimulated with IL-12 and IL-18, MAIT from GCA patients produced very high levels of IFN-γ and displayed a stronger proliferation compared with MAIT from controls (proliferation index 3.39 vs. 1.4; P = 0.032). In GCA, the functional characteristics of MAIT cells are modified toward a pro-inflammatory phenotype and a stronger proliferation capability in response to IL-12 and IL-18, suggesting that MAIT might play a role in GCA pathogenesis. Our results support the use of treatments targeting IL-12/IL-18 to inhibit the IFN-γ pathway in GCA.
Published: 2021

3. Giant-cell arteritis associated with myelodysplastic syndrome: French multicenter case control study and literature review

Author: Julien Rossignol, Hubert de Boysson, Anne Laure Roupie, Viviane Queyrel, Maud d'Aveni, Azeddine Dellal, Mathilde Versini, Eric Solary, François Maurier, Nicolas Schleinitz, J. Galland, Sara Thietart, J. Seguier, Olivier Decaux, Ygal Benhamou, Louis Terriou, Achille Aouba, Fabrice Carrat, Lise Willems, on behalf Minhemon, Maxime Samson, Arsène Mekinian, Pierre Fenaux, Olivier Fain, Matthieu Groh, Lionel Ades, Service de rhumatologie [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 de médecine interne [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), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Marseille, Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital Foch [Suresnes], Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpitaux Privés de Metz (HPMetz), Centre Hospitalier Universitaire [Rennes], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Département d'hématologie [Gustave Roussy], Institut Gustave Roussy (IGR), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hémato-oncologie [CHU Saint-Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Service de Médecine Interne (SOC 1 et SOC 2) [CHU de Dijon], and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_specialty, Immunology, Giant Cell Arteritis, Chronic myelomonocytic leukemia, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Recurrence, hemic and lymphatic diseases, Internal medicine, medicine, Immunology and Allergy, Humans, cardiovascular diseases, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Aged, 80 and over, business.industry, Incidence (epidemiology), Myelodysplastic syndromes, Case-control study, food and beverages, Middle Aged, medicine.disease, Myelodysplastic-Myeloproliferative Diseases, 3. Good health, Jaw claudication, Giant cell arteritis, 030104 developmental biology, Treatment Outcome, Myelodysplastic Syndromes, cardiovascular system, Anterior ischemic optic neuropathy, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Headaches, medicine.symptom, business
Abstract: Myelodysplastic syndromes (MDS) and MDS/myeloproliferative neoplasms (MDS/MPN) can be associated with giant cell arteritis (GCA). In this nationwide study by the "French Network of dysimmune disorders associated with hemopathies" (MINHEMON) the objective was to evaluate characteristics, treatment and outcome of GCA MDS-MDS/MPN.Retrospective analysis of patients that presented a MDS or MDS/MPN associated with GCA. Treatment efficiency, relapse-free and overall survival of GCA MDS-MDS/MPN were compared to GCA alone.Twenty-one patients with GCA MDS-MDS/MPN were included with median age 76 [42-92], M/F ratio 2.5, 8 MDS with multilineage dysplasia (38%), 4 chronic myelomonocytic leukemia (19%), at low or intermediate risk according to IPPS and IPSS-R. The prevalence of headaches, jaw claudication and anterior ischemic optic neuropathy was significantly lower in patients with GCA MDS-MDS/MPN compared to idiopathic GCA (14.3%, 0% and 0% versus 30%, 25%, and 25%, respectively; p .05). Other clinical and histology findings were similar. All GCA patients received steroid therapy as first-line treatment. Complete or partial response was observed in 14 GCA MDS-MDS/MPN patients (66.7%), of whom 6 (28.6%) received combined immunosuppressive therapies (versus 10% of idiopathic GCA; p = .07). Relapse incidence was similar in the two groups. Steroid dependence was more frequent among GCA MDS-MDS/MPN patients (12 (57%) versus 18 (22.5%); p .05). Relapse-free and steroid-free survivals were significantly decreased in GCA MDS-MDS/MPN patients (log rank 0.002 and 0.049 respectively), but not overall survival.Characteristics of GCA MDS-MDS/MPN seem different than idiopathic GCA, with a distinct clinical phenotype and poorer outcome with a higher risk of steroid dependence and relapse.
Published: 2020

4. Artérite à cellules géantes : de la physiopathologie aux nouvelles cibles thérapeutiques

Author: T. Ghesquiere, Hélène Greigert, Bernard Bonnotte, Maxime Samson, Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: 030203 arthritis & rheumatology, 0301 basic medicine, [SDV] Life Sciences [q-bio], 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, [SDV]Life Sciences [q-bio], General Medicine, 3. Good health
Abstract: Resume L’arterite a cellules geantes (ACG) est la plus frequente des vascularites de l’adulte. Il s’agit d’une vascularite granulomateuse, affectant les vaisseaux de gros calibre et survenant chez les patients de plus de 50 ans. La pierre angulaire du traitement de l’ACG reste a l’heure actuelle la corticotherapie, debutee entre 0,7 et 1 mg/kg/j en fonction de l’existence de complication(s) ischemique(s). Ce traitement est tres efficace, mais son sevrage est difficile, car associe a la survenue de rechutes qui contribuent a le poursuivre et a augmenter le risque de complications iatrogenes. Ainsi, des strategies d’epargne en corticoides doivent etre developpees. Des progres majeurs ont ete realises dans la comprehension de la physiopathologie de l’ACG ces dernieres annees. Le facteur declenchant reste a ce jour inconnu, mais les mecanismes conduisant a l’inflammation granulomateuse de la paroi vasculaire et a son remodelage, source des complications ischemiques de l’ACG, sont de mieux en mieux connus et ont permis l’emergence de nouvelles cibles therapeutiques, en particulier le blocage de l’activation du lymphocyte T, l’inhibition de la signalisation de l’interleukine-6 (IL-6), de l’IL-12/23 ou de l’IL-1β et dans un futur proche un meilleur controle du remodelage vasculaire.
Published: 2020

5. Une pseudotumeur rénale

Author: B. Nicolas, A Rajillah, A. Guilhem, Vanessa Leguy-Seguin, Bernard Bonnotte, T Thibault, T. Maldiney, M Chabannes, O Prevel, Sabine Berthier, Maxime Samson, Sylvain Audia, Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], and Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)
Subjects: 03 medical and health sciences, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Gastroenterology, Internal Medicine, Medicine, business
Published: 2019

6. Traitement de l’artérite à cellules géantes

Author: T. Ghesquiere, Bernard Bonnotte, Maxime Samson, Hélène Greigert, Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: 030203 arthritis & rheumatology, Gynecology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, [SDV]Life Sciences [q-bio], Medicine, 030212 general & internal medicine, General Medicine, business, 3. Good health
Abstract: Points essentiels En 2019, la corticotherapie reste le traitement de reference de l’arterite a cellules geantes (ACG) mais a condition de respecter des valeurs seuils concernant la decroissance des doses : 15 a 20 mg/j a 3 mois, 10 mg/j a 6 mois, 5 mg/j a 9–12 mois et sevrage en 12 a 18 mois. En cas de corticodependance a plus de 7,5 mg/j de prednisone ou d’intolerance de la corticotherapie, un traitement d’epargne en corticoides doit etre instaure, en premiere intention, methotrexate ou tocilizumab. Le choix d’un traitement d’epargne en corticoides doit prendre en consideration les caracteristiques individuelles du patient, les donnees d’efficacite disponibles concernant ce traitement, son cout et les modalites de suivi des patients. C’est pour cela que, sauf exception, nous utilisons d’abord le methotrexate et ensuite le tocilizumab. La prevention des evenements cardio-vasculaires est un element essentiel de la prise en charge des patients atteints d’ACG. Nous recommandons la prescription d’aspirine (75–100 mg/j) au cours du 1er mois de traitement et au long cours en cas de complication ischemique. Tout patient atteint d’ACG doit recevoir un traitement preventif de l’osteoporose selon les recommandations habituelles.
Published: 2019

7. Étude des lymphocytes T invariants au cours de l’artérite à cellules géantes

Author: Bernard Bonnotte, Sylvain Audia, Pierre-Henry Gabrielle, Maxime Samson, François Maurier, N. Vernier, Hervé Devilliers, Philip Bielefeld, T. Ghesquiere, H. Greigert, Paul Ornetti, Laurent Martin, Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de médecine interne et maladies systémiques (SOC 2) [CHU de Dijon], Service de médecine interne [hôpitaux privés de Metz], Hôpitaux Privés de Metz (HPMetz), Service de Rhumatologie (CHU de Dijon), Service d'Ophtalmologie (CHU de Dijon), and Laboratoire d’anatomie et cytologie pathologiques
Subjects: 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Gastroenterology, Internal Medicine, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 3. Good health, 030215 immunology
Abstract: Introduction L’arterite a cellules geantes (ACG) est une vascularite granulomateuse affectant les arteres de gros calibre et touchant les patients de plus de 50 ans. Les causes de l’ACG sont inconnues a ce jour ; cependant comme les MAIT (Mucosal associated invariant T lymphocytes), lymphocytes T caracterises par l’expression d’un TCR semi-invariant (TCRVα7.2) dont l’interaction est restreinte a MR1 (MHC related protein 1) [1] , semblent impliques au cours d’autres vascularites comme les vascularites associees aux ANCA [2] , nous avons analyse leurs caracteristiques quantitatives et fonctionnelles au cours de l’ACG. Materiels et methodes Apres signature d’un consentement eclaire, 27 patients atteints d’ACG au diagnostic et avant tout traitement (≥ 3/5 criteres ACR avec preuve histologique ou par imagerie de vascularite) et 16 sujets sains (absence de pathologie auto-immune, infectieuse, neoplasique et CRP ≤ 5 mg/L) ont ete inclus dans cette etude. Apres 3 mois de traitement par corticoides, un prelevement supplementaire a ete obtenu chez 20/27 patients. Les MAIT, definis par le phenotype CD3 + CD4-TCRγd-TCRVα7.2 + CD161 +, ont ete quantifies et phenotypes par cytometrie en flux. Pour l’etude de l’expression de l’IL-17 et l’IFN-γ, les cellules ont ete stimulees par PMA et Ionomycine en presence de brefeldine A (4 heures). Les donnees ont ete acquises sur un LSR II (BD Bioscience) et analysees avec Flowjo v10®. Les MAIT et les lymphocytes T (LT) CD161 + TCRVα7.2- ont ete isoles par Fluorescent Assisted Cell Sorting (FACS) puis cultives dans differentes conditions : aucune stimulation, billes anti-CD3/CD28, IL-12 et IL-18 (n = 4 patients et 5 temoins). Apres 7 jours, la proliferation cellulaire a ete mesuree par cytometrie en flux et l’index de proliferation calcule avec le logiciel ModFit®. Les coupes de biopsie d’arteres temporales positives ont ete etudiees par microscopie confocale (Leica TCS SP8). Les resultats sont exprimes en mediane [intervalle interquartile] et P est le resultat de tests de Mann–Whitney ou de Wilcoxon. Resultats Dans le sang, la frequence des MAIT parmi les LTαβ totaux etait comparable entre patients et temoins (0,48 [0,15–1,01] vs 0,47 [0,28–1,125] % ; p = 0,63) et n’etait pas modifiee par le traitement de l’ACG (0,48 [0,15–0,76] vs 0,43 [0,14–0,88] % ; p = 0,51). Le phenotype des MAIT etait modifie chez les patients : diminution de l’expression de CXCR3 (6,08 [1,57–13,96] vs 8,33 [6,13–36,66] % ; p = 0,048), augmentation de l’expression d’INF-γ (47,7 [31,8–66,7] vs 31,0 % [16,6–38,7] % ; p = 0.027). Le traitement par corticoides ne permettait pas de corriger ces anomalies phenotypiques des MAIT : respectivement (8,31 [3,90–16,3] vs 4,36 [1,64–17,47] % ; p = 0.96) et (39,8 [23,7–61,27] vs 42,4 [23,5–63,3,] % ; p = 0.85). A la difference des LT CD161 + TCRVα7.2-, les MAIT etaient capables de proliferer en presence d’IL-12 et d’IL-18 sans activation de leur TCR et a un niveau plus important chez les patients que chez les temoins : index de proliferation a 3,39 [2,36–7,15] vs 1,4 [1,2–2,42] ; (p = 0,032). Des MAIT, definies par le phenotype CD3 + IL-18R + TCRVα7.2 + ont ete identifies au sein des zones d’infiltrats en LT dans les arteres temporales de patients atteints d’ACG (n = 3). Discussion Meme si la frequence des MAIT n’est pas modifiee dans le sang des patients atteints d’ACG, leurs caracteristiques fonctionnelles sont modifiees vers un profil pro-inflammatoire cours de l’ACG : plus forte expression d’IFN-γ et plus forte proliferation en presence d’IL-12 et IL-18 sans activation de leur TCR. L’IL-12 et l’IL-18 etant 2 cytokines fortement exprimees dans les lesions d’ACG, nos resultats suggerent que les MAIT pourraient, en etant activees de facon independante de leur TCR, jouer un role dans l’amplification de la reponse inflammatoire au cours de l’ACG, ce d’autant que la corticotherapie ne permet pas de corriger le phenotype des MAIT. La diminution de l’expression de CXCR3 par les MAIT des patients atteints d’ACG pourrait etre liee au recrutement de MAIT CXCR3 + au sein des lesions de vascularite mais nos resultats ne permettent pas encore de le confirmer. Conclusion La modification du phenotype et des caracteristiques fonctionnelles des MAIT associes a leur presence dans les lesions de vascularite suggerent fortement que qu’ils jouent un role dans la physiopathologie de l’ACG.
Published: 2019

8. Venous thromboembolic events during warm autoimmune hemolytic anemia

Author: Bernard Bonnotte, Laurence Duvillard, Maxime Samson, Benoit Bach, Daniela Lakomy, Marine Branger, Sabine Berthier, Sylvain Audia, Jean Baptiste Bour, Marc Michel, Bénédicte Burlet, Julien Guy, Vanessa Leguy-Seguin, Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre de référence des maladies rares des cytopénies auto-immunes de l'adulte (CHU Dijon) (CRMR des cytopénies auto-immunes de l'adulte ), Laboratoire d'Immunologie et d'Immunothérapie des cancers [Dijon] (LIIC), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB), Laboratoire de sérologie-virologie (CHU de Dijon), Service d'hématologie biologique (CHU de Dijon), Service de Biochimie [CHU de Dijon], Service de médecine interne [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Hemolytic anemia, Male, Epidemiology, medicine.medical_treatment, lcsh:Medicine, Disease, 030204 cardiovascular system & hematology, Cardiovascular Medicine, Vascular Medicine, Biochemistry, Leukocyte Count, 0302 clinical medicine, Risk Factors, Medicine and Health Sciences, lcsh:Science, Multidisciplinary, Anemia, Venous Thromboembolism, Hematology, Middle Aged, Thrombosis, 3. Good health, Deep Vein Thrombosis, Oncology, Cardiovascular Diseases, Female, Autoimmune hemolytic anemia, Research Article, Adult, medicine.medical_specialty, Splenectomy, 03 medical and health sciences, Thrombotic manifestations, Diagnostic Medicine, Internal medicine, Thromboembolism, medicine, Cancer Detection and Diagnosis, Humans, Hemoglobin, cardiovascular diseases, Blood Coagulation, Aged, Retrospective Studies, Coagulation Disorders, business.industry, lcsh:R, Biology and Life Sciences, Proteins, Anticoagulants, Retrospective cohort study, Bilirubin, Odds ratio, medicine.disease, equipment and supplies, Auto-immune diseases (AID), Medical Risk Factors, Multivariate Analysis, lcsh:Q, Anemia, Hemolytic, Autoimmune, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology
Abstract: International audience; Thrombotic manifestations are a hallmark of many auto-immune diseases (AID), specially of warm autoimmune hemolytic anemia (wAIHA), as 15 to 33% of adults with wAIHA experience venous thromboembolic events (VTE). However, beyond the presence of positive antiphospholipid antibodies and splenectomy, risk factors for developing a VTE during wAIHA have not been clearly identified. The aim of this retrospective study was to characterize VTEs during wAIHA and to identify risk factors for VTE. Forty-eight patients with wAIHA were included, among whom 26 (54%) had secondary wAIHA. Eleven (23%) patients presented at least one VTE, that occurred during an active phase of the disease for 10/11 patients (90%). The frequency of VTE was not different between primary and secondary AIHA (23.7 vs. 19.2%; p = 0.5). The Padua prediction score based on traditional risk factors was not different between patients with and without VTE. On multivariate analysis, total bilirubin ≥ 40 μmol/L [odds ratio (OR) = 7.4; p = 0.02] and leucocyte count above 7x109/L (OR = 15.7; p = 0.02) were significantly associated with a higher risk of thrombosis. Antiphospholipid antibodies were screened in 9 out the 11 patients who presented a VTE and were negative. Thus, the frequency of VTE is high (23%) during wAIHA and VTE preferentially occur within the first weeks of diagnosis. As no clinically relevant predictive factors of VTE could be identified, the systematic use of a prophylactic anticoagulation should be recommended in case of active hemolysis and its maintenance after hospital discharge should be considered. The benefit of a systematic screening for VTE and its procedure remain to be determined.
Published: 2018

9. Altered distribution and function of splenic innate lymphoid cells in adult chronic immune thrombocytopenia

Author: Marion Ciudad-Bonté, Bernard Bonnotte, Thomas Moulinet, Olivier Facy, Sylvain Audia, Philippe Saas, Maxime Samson, Pablo Ortega-Deballon, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre de référence des maladies rares des cytopénies auto-immunes de l'adulte (CHU Dijon) (CRMR des cytopénies auto-immunes de l'adulte ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Université Bourgogne Franche-Comté [COMUE] (UBFC), and Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon)
Subjects: 0301 basic medicine, Adult, Male, medicine.medical_treatment, Immunology, Splenectomy, Gene Expression, Spleen, Innate lymphoid cells, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, Interferon-gamma, 0302 clinical medicine, Immune system, hemic and lymphatic diseases, medicine, Immunology and Allergy, Humans, Lymphocyte Count, Lymphocytes, skin and connective tissue diseases, Autoimmune disease, Purpura, Thrombocytopenic, Idiopathic, Innate immune system, Natural Cytotoxicity Triggering Receptor 2, business.industry, Macrophages, Innate lymphoid cell, Interleukin-2 Receptor alpha Subunit, Granulocyte-Macrophage Colony-Stimulating Factor, Cell Differentiation, Middle Aged, medicine.disease, Pathophysiology, Immunity, Innate, 3. Good health, Immune thrombocytopenia, 030104 developmental biology, medicine.anatomical_structure, Lymphatic system, Case-Control Studies, Female, business, 030215 immunology
Abstract: IF 7.607; International audience; Innate lymphoid cells (ILCs) have been characterized as innate immune cells capable to modulate the immune response in the mucosae. Human ILCs have been rarely described in secondary lymphoid organs except in tonsils. Moreover, their function and phenotype in human secondary lymphoid organs during autoimmune diseases have never been studied. We took advantage of splenectomy as a treatment of immune thrombocytopenia (ITP) to describe and compare splenic ILC from 18 ITP patients to 11 controls. We first confirmed that ILC3 represented the most abundant ILC subset in human non-inflamed spleens, accounting for 90% of total ILC, and that they were mostly constituted of NKp44- cells. On the contrary, proportions of ILC1 and ILC2 in spleens were lower than in blood. Splenic IL-2- and IFN-γ-producing ILC1 were increased in ITP. While the frequencies of total splenic ILC3 were similar in the two groups, splenic GM-CSF-producing ILC3 were increased in ITP. This is the first description of human ILC in a major secondary lymphoid organ during an autoimmune disease, ITP. We observed an expansion of splenic ILC1 that could participate to the Th1 skewing, while the increased production of GM-CSF by splenic ILC3 could stimulate splenic macrophages which play a key role in ITP pathophysiology.
Published: 2018

10. Large-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients

Author: Maxime Samson, Eric Liozon, Aurélie Daumas, David Saadoun, Mikael Ebbo, Bernard Bonnotte, Hubert de Boysson, A. Dumont, Boris Bienvenu, Alain Manrique, Marc Lambert, Audrey Sultan, Achille Aouba, Jean-Jacques Parienti, Mathieu Vautier, Service de médecine interne [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), Aix Marseille Université (AMU), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de Biostatistique et de Recherche Clinique (UBRC), Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Service de médecine interne [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Médecine Interne [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Service de médecine nucléaire [CHU Caen], Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, Giant Cell Arteritis, Immunology, Aortic Diseases, Large vessel, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Internal medicine, medicine, Humans, Immunology and Allergy, In patient, cardiovascular diseases, Arteritis, skin and connective tissue diseases, Aortic dilation, Aged, Retrospective Studies, 030203 arthritis & rheumatology, Giant-cell arteritis, business.industry, Aortitis Large-vessel involvement, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Giant cell arteritis, Increased risk, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Multicenter study, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cardiology, cardiovascular system, Female, business
Abstract: International audience; ObjectivesLarge-vessel involvement (LVI) can occur in giant-cell arteritis (GCA) and may represent a distinct disease subgroup with a higher risk for aortic dilation. This study aimed to better characterize the presentation and evolution of LVI in patients with GCA.Patients and methodsA retrospective multicenter study enrolled 248 GCA patients with LVI and 301 GCA patients without LVI on imaging. Factors associated with aortic dilation were identified in a multivariable model.ResultsThe patients with LVI were younger (p < 0.0001), more likely to be women (p = 0.01), and showed fewer cephalic symptoms (p < 0.0001) and polymyalgia rheumatica (p = 0.001) but more extracranial vascular symptoms (p = 0.05) than the patients without LVI. Glucocorticoids (GC) management did not differ between the two groups, but the GC discontinuation rate was lower in the patients with LVI (p = 0.0003). Repeated aortic imaging procedures were performed at 19 months [range: 5–162 months] and 17 months [range: 6–168 months] after diagnosis in 154 patients with LVI and 123 patients without LVI, respectively, of whom 21% and 7%, respectively, presented new aortic dilations (p = 0.0008). In the patients with LVI, aortic dilation occurred on an aorta segment shown to be inflammatory on previous imaging in 94% of patients. In the multivariate analysis, LVI was the strongest predictor of aortic dilation (hazard ratio: 3.16 [range: 1.34–7.48], p = 0.009).ConclusionsLVI represents a distinct disease pattern of GCA with an increased risk of aortic dilation. Control of the aortic morphology during follow-up is required.
Published: 2018

11. Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia

Author: Bernard Bonnotte, Annemieke G. Laarhoven, Kim Santegoets, Philippe Saas, Maxime Samson, Gestur Vidarsson, Sylvain Audia, Olivier Facy, Timothy R D J Radstake, Pablo Ortega-Deballon, Nona Janikashvili, Laboratory of Translational Immunology [Utrecht, the Netherlands], University Medical Center [Utrecht], Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Sanquin Research, University of Amsterdam [Amsterdam] (UvA), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Landsteiner Laboratory, University Medical Center Utrecht [the Netherlands] ( UMC Utrecht ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), University of Amsterdam [Amsterdam] ( UvA ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: Male, MESH: Spleen, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], MESH : Aged, MESH: Flow Cytometry, Immunoglobulin G, 0302 clinical medicine, MESH : Antigens, CD86, MESH: Autoimmune Diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, CD86, MESH: Immunoglobulins, Intravenous, MESH : Receptors, IgG, MESH : Macrophages, MESH: Immunoglobulin G, MESH: Middle Aged, Immunoglobulins, Intravenous, Flow Cytometry, macrophages, MESH : Phenotype, Splenectomy, Antibody, IgG, Phagocytosis, Immunology, Immunoglobulins, Spleen, MESH: Receptors, IgG, MESH: Phenotype, MESH: Splenectomy, 03 medical and health sciences, MESH : Autoimmune Diseases, Genetic, MESH: Polymorphism, Genetic, Humans, MESH : Middle Aged, Polymorphism, Aged, Polymorphism, Genetic, MESH: Humans, Macrophages, MESH : Humans, MESH: Adult, 030104 developmental biology, spleen, B7-2 Antigen, MESH: Female, 0301 basic medicine, MESH : Polymorphism, Genetic, Receptor expression, medicine.disease_cause, Autoimmunity, immune system diseases, hemic and lymphatic diseases, Receptors, Immunology and Allergy, MESH : Female, MESH: Phagocytosis, MESH: Aged, biology, MESH : Thrombocytopenia, Fc receptors, autoimmunity, MESH : Adult, Middle Aged, Antigens, CD86, medicine.anatomical_structure, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Immunoglobulins, Intravenous, Intravenous, MESH : Spleen, Adult, MESH : Immunoglobulin G, MESH : Flow Cytometry, MESH : Male, chemical and pharmacologic phenomena, MESH: Antigens, CD86, Autoimmune Diseases, All institutes and research themes of the Radboud University Medical Center, MESH : Phagocytosis, medicine, Journal Article, Antigens, Opsonin, MESH : Splenectomy, MESH: Thrombocytopenia, Receptors, IgG, MESH: Macrophages, Original Articles, Thrombocytopenia, MESH: Male, biology.protein, 030215 immunology
Abstract: Summary Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcγR expression were measured by flow cytometry on splenic macrophages. The major FcγR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcγR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2 weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcγRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcγR expression on splenic macrophages but decreases their phagocytic capabilities.
Published: 2017

12. T cell Polarization toward T(H)2/T(FH)2 and T(H)17/T(FH)17 in Patients with IgG4-related Disease

Author: S. Palat, Nathalie Costedoat-Chalumeau, Alexis Régent, François Maurier, Catherine Farnarier, Anderson Loundou, Jean-Robert Harlé, Julie Graveleau, Bernard Bonotte, Aurélie Grados, Maxime Samson, Mikael Ebbo, Benjamin Terrier, Emmanuelle Bernit, Christelle Piperoglou, Mohamed Hamidou, Nathalie Morel, Nicolas Schleinitz, Frédéric Vély, Matthieu Groh, Sylvain Audia, Amandine Forestier, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie [Hôpital de la Conception - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Paris 5 (UPD5), 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), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Immunologie - Immunopathologie - Immunothérapeutique (I3), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité d'Aide Méthodologique, Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratory of Translational Immunology [Utrecht, the Netherlands], University Medical Center [Utrecht], Service de médecine interne, Hôpital Sainte-Blandine-Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Centre hospitalier de Saint-Nazaire, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service de Chirurgie, Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Service d'Immunologie [AP-HM], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville)-Hôpital Sainte-Blandine, Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Université de Franche-Comté (UFC)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Hôpital de la Conception [CHU - APHM] (LA CONCEPTION ), and Assistance Publique - Hôpitaux de Marseille (APHM)-Hospices Civiles de Marseille-Hôpital de la Conception [CHU - APHM] (LA CONCEPTION )
Subjects: 0301 basic medicine, medicine.medical_treatment, T cell, Immunology, plasmablasts, Biology, CXCR3, Peripheral blood mononuclear cell, Flow cytometry, 03 medical and health sciences, Interleukin 21, T helper cells, medicine, Immunology and Allergy, Cytotoxic T cell, IgG4-related disease, B cell, medicine.diagnostic_test, 3. Good health, 030104 developmental biology, Cytokine, medicine.anatomical_structure, Sjögren’s syndrome, T follicular helper cells, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: International audience; IgG4-related disease (IgG4-RD) is a fibro-inflammatory disorder involving virtually every organ with a risk of organ dysfunction. Despite recent studies regarding B cell and T cell compartments, the disease's pathophysiology remains poorly understood. We examined and characterized subsets of circulating lymphocytes in untreated patients with active IgG4-RD. Twenty-eight consecutive patients with biopsy-proven IgG4-RD were included in a prospective, multicentric study. Lymphocyte's subsets were analyzed by flow cytometry, with analysis of T(H)1/T(H)2/T(H)17, T-FH cells, and cytokine release by peripheral blood mononuclear cells. Results were compared to healthy controls and to patients with primary Sjogren's syndrome. Patients with IgG4-RD showed an increase of circulating T regulatory, T(H)2, T(H)17, and CD4(+)CXCR5(+)PD1(+) TFH cell subsets. Accordingly, increased levels of IL-10 and IL-4 were measured in IgG-RD patients. TFH increase was characterized by the specific expansion of T(FH)2 (CCR6(-)CXCR3(-)), and to a lesser extent of (T(FH)17 (CCR6(+)CXCR3(-))) cells. Interestingly, CD4(+)CXCR5(+)PD1(+) TFH cells normalized under treatment. IgG4-RD is characterized by a shift of circulating T cells toward a T(H)2/T(FH)2 and T(H)17/T(FH)17 polarization. This immunological imbalance might be implicated in the disease's pathophysiology. Treatment regimens targeting such T cells warrant further evaluation.
Published: 2017

13. Endovascular stent placement for chronic post-thrombotic symptomatic ilio-femoral venous obstructive lesions: a single-center study of safety, efficacy and quality-of-life improvement

Author: Christophe Galland, Bernard Bonnotte, Marco Midulla, Serge Aho-Glélé, Maxime Samson, Emmanuel Demaistre, Marie-Tiphaine Falcoz, Béatrice Terriat, Romaric Loffroy, Pierre Pottecher, Olivier Chevallier, Sylvain Favelier, Sylvain Audia, Nicolas Falvo, Laboratoire Electronique, Informatique et Image ( Le2i ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Service d'angiologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Département d' Epidémiologie, statistiques et recherche clinique, Service d'hématologie biologique (CHU de Dijon), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Laboratoire Electronique, Informatique et Image [UMR6306] (Le2i), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Arts et Métiers (ENSAM), Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-Arts et Métiers Sciences et Technologies, HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Bourgogne (UB)-École Nationale Supérieure d'Arts et Métiers (ENSAM), and HESAM Université (HESAM)-HESAM Université (HESAM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)
Subjects: endovascular treatment, medicine.medical_specialty, Ilio-femoral venous obstructive lesion, Chronic venous insufficiency, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, medicine.medical_treatment, Deep vein, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030204 cardiovascular system & hematology, Iliac Vein, Single Center, 030218 nuclear medicine & medical imaging, law.invention, [ SDV.IB.MN ] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Validation, medicine, Radiology, Nuclear Medicine and imaging, Disease, Clinical-Experience, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, post-thrombotic syndrome (PTS), [ SDV.IB.IMA ] Life Sciences [q-bio]/Bioengineering/Imaging, Reporting Standards, business.industry, Deep-Vein Thrombosis, Thrombolysis, Outflow, medicine.disease, Thrombosis, 3. Good health, Surgery, Management, medicine.anatomical_structure, stent placement, quality of life, Controlled-Trial, Original Article, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Radiology, Complication, business, Cohort study
Abstract: International audience; Background: Post-thrombotic syndrome (PTS) is a frequent complication of deep vein thrombosis (DVT) despite adequate treatment. Venous angioplasty and stent placement has been progressively used to restore and maintain venous patency in PTS patients. This study reports our single-center experience with the use of endovascular treatment for chronic post-thrombotic symptomatic ilio-femoral venous obstructive lesions. Methods: A prospective mono-centric observational cohort study of PTS patients with chronic symptomatic ilio-femoral venous obstructive lesions referred for endovascular treatment was conducted from March 2012 to April 2016. Procedure consisted in recanalization, pre-dilation and self-expandable stenting of stenotic or occluded iliac and/or femoral veins. Severity of PTS, quality-of-life and treatment outcomes were assessed using Villalta scale and Chronic Venous Insufficiency Questionnaire (CIVIQ-20) at baseline and 3 months after the procedure. Imaging follow-up was based on duplex ultrasound (US) and computed tomography (CT). Results: Twenty-one patients (11 females, 10 males; median age, 41 years; range, 32-60) were included. Recanalization and stenting was successfully accomplished in all prime procedures, 4 patients benefitted from an additional procedure. Immediate technical success rate was 96% considering 25 procedures, performed without any complications. Median follow-up was 18 months (range, 6-30 months) with a 90.5% stent patency rate. Villalta score significantly decreased from baseline compared with 3 months after the procedure [14 (range, 11-22) and 5 (range, 1-10), respectively, P
Published: 2016

14. Comparison of idiopathic (isolated) aortitis and giant cell arteritis-related aortitis. A French retrospective multicenter study of 117 patients

Author: F. Perrin, Pierre Pottier, Maxime Samson, Thomas Le Gallou, Pascal Roblot, Anabele Dos Santos, Mohamed Hamidou, Alexandra Espitia-Thibault, Jérôme Connault, Olivier Espitia, Christian Lavigne, Hervé Maisonneuve, Jean M. Brisseau, Jean Michel Serfaty, Patrick Jego, Julie Graveleau, Philippe Moreau, Claire de Moreuil, Georges Fau, François Maillot, Cédric Landron, Cécile Durant, Agathe Masseau, Elisabeth Diot, Cristina Belizna, M. Artifoni, Julie Magnant, Antoine Néel, Christian Agard, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Service de Médecine Interne, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Internal Medicine B Unit, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine interne et immunologie clinique [Rennes] = internal medicine and clinical immunology [Rennes], CHU Pontchaillou [Rennes], GIRC Thrombose, Service de médecine interne [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), CH Vannes, Centre hospitalier de Saint-Nazaire, CH de Lorient, Service d'hématologie, Centre hospitalier La Roche-Sur-Yon, 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), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), 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 hospitalier universitaire de Nantes ( CHU Nantes ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ), Centre hospitalier universitaire de Poitiers ( CHU Poitiers ), CHU Angers, CHRU Tours, Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Nutrition, croissance et cancer (U 1069) ( N2C ), Université de Tours-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de médecine interne, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Sud, Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), unité de recherche de l'institut du thorax UMR1087 UMR6291 ( ITX ), Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Brenner, Nelly, and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: medicine.medical_specialty, idiopathic aortitis, Immunology, 030204 cardiovascular system & hematology, 03 medical and health sciences, Aortic aneurysm, 0302 clinical medicine, Aneurysm, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine, Humans, Immunology and Allergy, In patient, cardiovascular diseases, Aortitis, Aged, Retrospective Studies, 030203 arthritis & rheumatology, business.industry, giant cell arteritis, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Prognosis, medicine.disease, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Surgery, Aortic wall, Dissection, Giant cell arteritis, Multicenter study, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, isolated aortitis, cardiovascular system, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, aortic aneurysm
Abstract: International audience; Objectives: The aim of the study was to compare clinical/imaging findings and outcome in patients with idiopathic (isolated aortitis, IA) and with giant cell arteritis (GCA)-related aortitis.Methods: Patients from 11 French internal medicine departments were retrospectively included. Aortitis was defined by aortic wall thickening > 2 mm and/or an aortic aneurysm on CT-scan, associated to inflammatory syndrome. Patients with GCA had at least 3 ACR criteria. Aortic events (aneurysm, dissection, aortic surgeries) were reported, and free of aortic events-survival were compared.Results: Among 191 patients with non-infectious aortitis, 73 with GCA and 44 with IA were included. Patients with IA were younger (65 vs 70y, p = 0.003) and comprised more past/current smokers (43 vs 15%, p = 0.0007). Aortic aneurisms were more frequent (38% vs 20%, p = 0.03) and aortic wall thickening was more pronounced in IA. During follow-up (median = 34 months), subsequent development of aortic aneurysm was significantly lower in GCA when compared to IA (p = 0.009). GCA patients required significantly less aortic surgery during follow-up than IA patients (p = 0.02). Mean age, sex-ratio, inflammatory parameters and free of aortic aneurism-survival were equivalent in patients with IA ≥ 60y when compared to patients with GCA-related aortitis.Conclusions: IA is more severe than aortitis related to GCA, with higher proportions of aortic aneurism at diagnosis and during follow-up. IA is a heterogeneous disease and its prognosis is worse in younger patients < 60y. Most patients with IA ≥ 60y share many features with GCA-related aortitis.
Published: 2016

15. Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis

Author: Patrick Manckoundia, Jean Francis Maillefert, Luc Mouthon, Malika Trad, Laurent Martin, Jennifer Fraszczak, Sylvain Audia, Nicolas Larmonier, Julien Vinit, Philippe Saas, Marion Ciudad, Bernard Bonnotte, Serge Aho-Glélé, Jean François Besancenot, V. Leguy, Daniela Lakomy, Nona Janikashvili, Loïc Guillevin, Sabine Berthier, Bernard Lorcerie, Maxime Samson, Nils Olivier Olsson, Andrew Bateman, Paul Ornetti, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Dijon, Steele Children's Research Center, University of Arizona, Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Southampton General Hospital, Saas, Philippe, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université Paris Descartes - Paris 5 ( UPD5 ), and CHU Cochin [AP-HP]
Subjects: Male, Pathology, MESH: Th17 Cells, Cell, MESH : Aged, MESH : Prospective Studies, MESH: Flow Cytometry, T-Lymphocytes, Regulatory, Pathogenesis, MESH : T-Lymphocytes, Regulatory, 0302 clinical medicine, immune system diseases, MESH : Th1 Cells, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Pharmacology (medical), MESH : Female, Prospective Studies, skin and connective tissue diseases, Cells, Cultured, MESH: Aged, 0303 health sciences, MESH: Middle Aged, medicine.diagnostic_test, MESH: Giant Cell Arteritis, Cell Differentiation, MESH : Adult, Middle Aged, Flow Cytometry, MESH : NK Cell Lectin-Like Receptor Subfamily B, 3. Good health, MESH: NK Cell Lectin-Like Receptor Subfamily B, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Vasculitis, MESH : Cell Differentiation, Glucocorticoid, medicine.drug, NK Cell Lectin-Like Receptor Subfamily B, MESH: Cells, Cultured, Adult, MESH: Cell Differentiation, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH : Flow Cytometry, T cell, MESH : Male, Immunology, Giant Cell Arteritis, Biology, Polymyalgia rheumatica, 03 medical and health sciences, Rheumatology, Biopsy, MESH : Cells, Cultured, medicine, MESH : Th17 Cells, Humans, MESH : Middle Aged, 030304 developmental biology, Aged, 030203 arthritis & rheumatology, MESH: Humans, MESH: T-Lymphocytes, Regulatory, MESH : Humans, MESH: Adult, Th1 Cells, medicine.disease, MESH : Giant Cell Arteritis, MESH: Prospective Studies, MESH: Male, Giant cell arteritis, MESH: Th1 Cells, Polymyalgia Rheumatica, MESH: Polymyalgia Rheumatica, Th17 Cells, MESH : Polymyalgia Rheumatica, MESH: Female
Abstract: International audience; OBJECTIVE: Giant cell arteritis (GCA) is the most frequently occurring vasculitis in elderly individuals, and its pathogenesis is not fully understood. The objective of this study was to decipher the role of the major CD4+ T cell subsets in GCA and its rheumatologic form, polymyalgia rheumatica (PMR). METHODS: A prospective study of the phenotype and the function of major CD4+ T cell subsets (Th1, Th17, and Treg cells) was performed in 34 untreated patients with GCA or PMR, in comparison with 31 healthy control subjects and with the 27 treated patients who remained after the 7 others withdrew. RESULTS: Compared with control subjects, patients with GCA and patients with PMR had a decreased frequency of Treg cells and Th1 cells, whereas the percentage of Th17 cells was significantly increased. Furthermore, an analysis of temporal artery biopsy specimens obtained from patients affected by GCA for whom biopsy results were positive demonstrated massive infiltration by Th17 and Th1 lymphocytes without any Treg cells. After glucocorticoid treatment, the percentages of circulating Th1 and Th17 cells decreased, whereas no change in the Treg cell frequency was observed. The frequency of CD161+CD4+ T cells, which are considered to be Th17 cell precursors, was similar in patients and control subjects. However, these cells highly infiltrated GCA temporal artery biopsy specimens, and their ability to produce interleukin-17 in vitro was significantly enhanced in patients with GCA and patients with PMR and was correlated with a decrease in the phosphorylated form of STAT-1. CONCLUSION: This study is the first to demonstrate that the frequency of Treg cells is decreased in patients with GCA and patients with PMR, and that CD161+CD4+ T lymphocytes, differentiated into Th1 cells and Th17 cells, are involved in the pathogenesis of GCA and PMR.
Published: 2012

16. Cytotoxic Dendritic Cells Generated from Cancer Patients

Author: Salem Chouaib, Pascal Foucher, Jennifer Fraszczak, Bernard Bonnotte, Denis Caillot, Sylvain Audia, Marion Ciudad, Catherine Vergely, Daniela Lakomy, Maxime Samson, Malika Trad, Julien Vinit, Emmanuel Katsanis, Laurent Lagrost, Nicolas Larmonier, Nona Janikashvili, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), IFR100 - Structure fédérative de recherche Santé-STIC, Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Cytokines et Immunologie des Tumeurs Humaines (U753), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), University of Arizona, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés ( TRACES ), École des hautes études en sciences sociales ( EHESS ) -Université Toulouse - Jean Jaurès ( UT2J ) -Ministère de la Culture et de la Communication ( MCC ) -Institut national de recherches archéologiques préventives ( Inrap ) -Centre National de la Recherche Scientifique ( CNRS ), Cytokines et Immunologie des Tumeurs Humaines ( U753 ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut Gustave Roussy ( IGR ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Steele Children's Research Center, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Travaux et recherches archéologiques sur les cultures, les espaces et les sociétés (TRACES), École des hautes études en sciences sociales (EHESS)-Université Toulouse - Jean Jaurès (UT2J)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Vergely, Catherine, Immunologie intégrative des tumeurs et immunothérapie des cancers (INTIM), and Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay
Subjects: Cytotoxicity, Immunologic, Lipopolysaccharides, MESH: Immunotherapy, medicine.medical_treatment, T-Lymphocytes, [SDV]Life Sciences [q-bio], MESH : Cytotoxicity, Immunologic, MESH: Flow Cytometry, MESH : Lipopolysaccharides, Lymphocyte Activation, 0302 clinical medicine, Cancer immunotherapy, Neoplasms, Immunology and Allergy, Cytotoxic T cell, MESH: Neoplasms, Cytotoxicity, MESH : Peroxynitrous Acid, MESH: Peroxynitrous Acid, 0303 health sciences, MESH: Dendritic Cells, hemic and immune systems, Flow Cytometry, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Immunotherapy, Immunotherapy, MESH : Flow Cytometry, Immunology, chemical and pharmacologic phenomena, Biology, Article, 03 medical and health sciences, Immune system, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Peroxynitrous Acid, medicine, Humans, MESH: Cytotoxicity, Immunologic, MESH: Lymphocyte Activation, MESH : Lymphocyte Activation, 030304 developmental biology, MESH : T-Lymphocytes, MESH: Humans, Follicular dendritic cells, [ SDV ] Life Sciences [q-bio], MESH : Humans, Cancer, Dendritic Cells, medicine.disease, MESH : Neoplasms, MESH: T-Lymphocytes, MESH : Dendritic Cells, Cancer cell, MESH: Lipopolysaccharides, 030215 immunology
Abstract: Known for years as professional APCs, dendritic cells (DCs) are also endowed with tumoricidal activity. This dual role of DC as killers and messengers may have important implications for tumor immunotherapy. However, the tumoricidal activity of DCs has mainly been investigated in animal models. Cancer cells inhibit antitumor immune responses using numerous mechanisms, including the induction of immunosuppressive/ tolerogenic DCs that have lost their ability to present Ags in an immunogenic manner. In this study, we evaluated the possibility of generating tumor killer DCs from patients with advanced-stage cancers. We demonstrate that human monocyte-derived DCs are endowed with significant cytotoxic activity against tumor cells following activation with LPS. The mechanism of DC-mediated tumor cell killing primarily involves peroxynitrites. This observed cytotoxic activity is restricted to immature DCs. Additionally, after killing, these cytotoxic DCs are able to activate tumor Ag-specific T cells. These observations may open important new perspectives for the use of autologous cytotoxic DCs in cancer immunotherapy strategies.
Published: 2012

17. 'Do hip OA patients referred to orthopedic surgeons by general practitioners and rheumatologists differ?'

Author: Jean-Francis Maillefert, Carine Roy, Maxime Samson, Philippe Ravaud, Christian Cadet, Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer (U866) (LNC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bourgogne (UB)-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA)
Subjects: Male, Rural Population, ''TOTAL JOINT REPLACEMENT, Multivariate analysis, Arthroplasty, Replacement, Hip, DETERMINANTS, Osteoarthritis, Hip, 0302 clinical medicine, immune system diseases, Surveys and Questionnaires, TOTAL JOINT REPLACEMENT, 030212 general & internal medicine, Practice Patterns, Physicians', skin and connective tissue diseases, OUTCOMES, General Medicine, Middle Aged, KNEE ARTHROPLASTIES, 3. Good health, FUNCTIONAL STATUS, [ SCCO.NEUR ] Cognitive science/Neuroscience, Female, Functional status, Multivariate statistical, Total hip arthroplasty, musculoskeletal diseases, medicine.medical_specialty, 03 medical and health sciences, Rheumatology, General Practitioners, Physicians, Internal medicine, RATES'', medicine, Hip osteoarthritis, Humans, Total joint replacement, RATES, Aged, 030203 arthritis & rheumatology, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Orthopedics, OSTEOARTHRITIS, Multivariate Analysis, Orthopedic surgery, Physical therapy, RISK-FACTORS, business
Abstract: Samson, Maxime | Maillefert, Jean-Francis | Roy, Carine | Cadet, Christian | Ravaud, Philippe; International audience; ''There is no consensus regarding indications for total hip arthroplasty (THA) in hip osteoarthritis (OA). Patients can be referred to surgeons either by a general practitioner (GP) or a rheumatologist. The aim of this study was to determine whether patients referred to orthopedic surgeons by GP and rheumatologists differed. GPs and rheumatologists were asked to include one patient suffering from hip OA for whom a consultation with a surgeon was planned to determine if THA was indicated. Surgeons' decisions were obtained by follow-up questionnaires. Univariate and then multivariate statistical analysis evaluated differences between patients referred by GPs and those referred by rheumatologists. A total of 558 patients were included. THA was prescribed in 71.6 % of patients referred by rheumatologists vs. 57.6 % of patients referred by GPs (p = 0.008). Patients referred by rheumatologists were younger (66.3 vs. 69.3 years; p = 0.006), less frequently retired (72.9 vs. 84.2 %; p = 0.007), and presented with a higher New Zealand score (54.3 vs. 48.1; p = 0.0009). On multivariate analysis, the variables related to patients referred by rheumatologists were the SF-12 mental score, the New Zealand score, and the surgeon's decision. Patients consulting a surgeon to discuss THA were more likely to be operated on when referred by a rheumatologist, which might be due to differences in the rheumatologists' and GPs' opinions on the right time to perform surgery or due to differences in the populations followed by rheumatologists and GPs, those followed by rheumatologists being younger, more active, more urban, with a greater willingness to undergo surgery.''
Published: 2012

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17 results on '"Maxime Samson"'

1. Hematological malignancies in giant cell arteritis: a french population-based study

2. Mucosal-associated invariant T cells in giant cell arteritis

3. Giant-cell arteritis associated with myelodysplastic syndrome: French multicenter case control study and literature review

4. Artérite à cellules géantes : de la physiopathologie aux nouvelles cibles thérapeutiques

5. Une pseudotumeur rénale

6. Traitement de l’artérite à cellules géantes

7. Étude des lymphocytes T invariants au cours de l’artérite à cellules géantes

8. Venous thromboembolic events during warm autoimmune hemolytic anemia

9. Altered distribution and function of splenic innate lymphoid cells in adult chronic immune thrombocytopenia

10. Large-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients

11. Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia

12. T cell Polarization toward T(H)2/T(FH)2 and T(H)17/T(FH)17 in Patients with IgG4-related Disease

13. Endovascular stent placement for chronic post-thrombotic symptomatic ilio-femoral venous obstructive lesions: a single-center study of safety, efficacy and quality-of-life improvement

14. Comparison of idiopathic (isolated) aortitis and giant cell arteritis-related aortitis. A French retrospective multicenter study of 117 patients

15. Th1 and Th17 lymphocytes expressing CD161 are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis

16. Cytotoxic Dendritic Cells Generated from Cancer Patients

17. 'Do hip OA patients referred to orthopedic surgeons by general practitioners and rheumatologists differ?'

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