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1. Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians?

Author: Kevin Didier, Loïs Bolko, Delphine Giusti, Segolene Toquet, Ailsa Robbins, Frank Antonicelli, Amelie Servettaz, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 ( IRMAIC ), and Université de Reims Champagne-Ardenne ( URCA )
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, rheumatoid arthritis, Anti-nuclear antibody, dermatomyositis, systemic sclerosis, Immunology, Antisynthetase syndrome, Disease, Review, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, systemic lupus erythematosus, antibody, medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Humans, Connective Tissue Diseases, Myositis, Autoantibodies, 030203 arthritis & rheumatology, business.industry, necrotizing myopathy, Autoantibody, Dermatomyositis, medicine.disease, 3. Good health, 030104 developmental biology, Rheumatoid arthritis, Sjögren’s syndrome, [SDV.IMM]Life Sciences [q-bio]/Immunology, antisynthetase syndrome, business, lcsh:RC581-607
Abstract: International audience; Connective tissue diseases (CTDs) such as systemic lupus erythematosus, systemic sclerosis, myositis, Sjögren's syndrome, and rheumatoid arthritis are systemic diseases which are often associated with a challenge in diagnosis. Autoantibodies (AAbs) can be detected in these diseases and help clinicians in their diagnosis. Actually, pathophysiology of these diseases is associated with the presence of antinuclear antibodies. In the last decades, many new antibodies were discovered, but their implication in pathogenesis of CTDs remains unclear. Furthermore, the classification of these AAbs is nowadays misused, as their targets can be localized outside of the nuclear compartment. Interestingly, in most cases, each antibody is associated with a specific phenotype in CTDs and therefore help in better defining either the disease subtypes or diseases activity and outcome. Because of recent progresses in their detection and in the comprehension of their pathogenesis implication in CTD-associated antibodies, clinicians should pay attention to the presence of these different AAbs to improve patient's management. In this review, we propose to focus on the different phenotypes and features associated with each autoantibody used in clinical practice in those CTDs.
Published: 2018

2. Anti-Type VII Collagen Antibodies Are Identified in a Subpopulation of Bullous Pemphigoid Patients With Relapse

Author: Giusti , Delphine, Gatouillat , Grégory, Le Jan , Sébastien, Plée , Julie, Bernard , Philippe, Antonicelli , Frank, Pham , Bach-Nga, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 ( IRMAIC ), Université de Reims Champagne-Ardenne ( URCA ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: Male, bullous pemphigoid, Collagen Type VII, [SDV]Life Sciences [q-bio], Immunology, Enzyme-Linked Immunosorbent Assay, epitope spreading, Recurrence, mucous membrane involvement, Pemphigoid, Bullous, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, ComputingMilieux_MISCELLANEOUS, Aged, Autoantibodies, Retrospective Studies, Skin, Original Research, Aged, 80 and over, relapse, Mucous Membrane, Middle Aged, anti-type VII collagen antibodies, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Bullous pemphigoid (BP) is an autoimmune bullous skin disease characterized by anti-BP180 and anti-BP230 autoantibodies (AAbs). Mucous membrane involvement is an uncommon clinical feature of BP which may evoke epidermolysis bullosa acquisita, another skin autoimmune disease characterized by anti-type VII collagen AAbs. We therefore evaluated the presence of anti-type VII collagen AAbs in the serum of BP patients with and without mucosal lesions at time of diagnosis and under therapy. Anti-BP180, anti-BP230, and anti-type VII collagen AAbs were measured by ELISA in the serum of unselected patients fulfilling clinical and histo/immunopathological BP criteria at baseline (n = 71) and at time of relapse (n = 24). At baseline, anti-type VII collagen AAbs were detected in 2 out of 24 patients with BP presenting with mucosal involvement, but not in patients without mucosal lesions (n = 47). At the time of relapse, 10 out of 24 BP patients either displayed a significant induction or increase of concentrations of anti-type VII collagen AAbs (P
Published: 2018

3. Mucosal Involvement in Bullous Pemphigoid Is Mostly Associated with Disease Severity and to Absence of Anti-BP230 Autoantibody

Author: Clapé, Ariane, Muller, Céline, Gatouillat, Grégory, Le Jan, Sébastien, Barbe, Coralie, Pham, Bach-Nga, Antonicelli, Frank, Bernard, Philippe, Immunodermatologie, Cytokines, Cancer - EA 7319 ( ICA ), Université de Reims Champagne-Ardenne ( URCA ), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 ( IRMAIC ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Immunodermatologie, Cytokines, Cancer - EA 7319 (ICA), Université de Reims Champagne-Ardenne (URCA), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: Aged, 80 and over, Male, anti-BP230, bullous pemphigoid, Mucous Membrane, integumentary system, BP Disease Area Index, Dystonin, autoantibodies, Immunology, Severity of Illness Index, Pemphigoid, Bullous, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Female, mucosal involvement, skin and connective tissue diseases, [ SDV.MHEP.DERM ] Life Sciences [q-bio]/Human health and pathology/Dermatology, Immunity, Mucosal, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Original Research, Aged
Abstract: International audience; Bullous pemphigoid (BP) is the most common autoimmune bullous disease and typically affects the elderly. Binding of specific autoantibodies to BP180/230 hemidesmosomal components induces an inflammatory response leading to skin blister formation. Unusual manifestations of BP include additional mucous membrane involvement, without pathophysiological knowledge associated to the formation of these lesions. We here performed a prospective study on series of consecutive BP patients with (n = 77) and without (n = 18) mucosal involvements at baseline to further investigate why some BP patients display mucosal lesion and other not. Analysis of disease activity showed that BP patients with mucosal involvement displayed a higher total BP Disease Area Index (BPDAI) score (P = 0.008), but also higher skin and blister/erosion BPDAI scores (P = 0.02 and P = 0.001, respectively). By contrast, the erythema/urticaria BPDAI score was identical between the two groups of patients. The erythema/urticaria BPDAI score, but not the blister/erosion BPDAI score, was correlated with the serum concentration of anti-BP180 NC16A autoantibodies in patients with mucosal involvement. In multivariate analysis, the absence of anti-BP230 autoantibody was the only factor independently associated with mucosal involvement (OR 7.8; 95% CI, 3.1-19.6) (P
Published: 2018

4. Efficacy and safety of combination targeted therapies in immune-mediated inflammatory disease: the COMBIO study

Author: Lucas Guillo, Benoit Flachaire, Jérôme Avouac, Catherine Dong, Maria Nachury, Guillaume Bouguen, Anthony Buisson, Ludovic Caillo, Mathurin Fumery, Cyrielle Gilletta, Xavier Hébuterne, Pierre Lafforgue, David Laharie, Emmanuel Mahé, Hubert Marotte, Stéphane Nancey, Sébastien Ottaviani, Jean-Hugues Salmon, Guillaume Savoye, Mélanie Serrero, Mathieu Uzzan, Manuelle Viguier, Christophe Richez, Laurent Peyrin-Biroulet, Philipe Seksik, Thao Pham, Philippe Ah-Soune, Nadia Arab, Laurent Beaugerie, Loïs Bolko, Joelle Bonnet, Yoram Bouhnik, Anne Bourrier, Franck Brazier, Franck Carbonnel, Maeva Charkaoui, Isabelle Charlot-Lambrecht, Antoine Chupin, Alice Combier, Marion Couderc, Fabienne Coury-Lucas, Ariadne Desjeux, Nicolas Duveau, Anne Grasland, Jean-Charles Grimaud, Xavier Guennoc, Cécilia Landman, Isabelle Nion-Larmurier, Catherien Leberre, Romain Leenhardt, Aude Le Goffic, Henri Montaudie, Jacques Morel, Thierry Passeron, Jeanne-Marie Perotin Collard, Elodie Poisnel, Vincent Pradel, Martin Soubrier, Harry Sokol, Eric Toussirot, Caroline Trang, My-Linh Trans Minh, Sophie Trijau, Frank Verhoeven, Stéphanie Viennot, Daniel Wendling, Hôpital Nord [CHU - APHM], Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Clermont-Ferrand, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, CHU Amiens-Picardie, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Institut du Mouvement et de l’appareil Locomoteur [Hôpital Sainte-Marguerite - APHM] (IML), Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud )-Rhumatologie [Sainte- Marguerite - APHM] ( Hôpitaux Sud), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Centre Hospitalier Victor Dupouy, Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Reims (CHU Reims), Vieillissement, Fragilité (VIEFRA - EA 3797), Université de Reims Champagne-Ardenne (URCA), Nutrition, Inflammation et axe Microbiote-Intestin-Cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Beaujon [AP-HP], Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Hôpital universitaire Robert Debré [Reims], Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Rhumatologie [CHU Pellegrin], Groupe hospitalier Pellegrin, Centre National de Référence des Maladies Auto-Immunes Systémiques Rares de l'Est et du Sud-Ouest (RESO), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), 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), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Hôpital Charles Nicolle [Rouen]-CHU Rouen
Subjects: Adult, Cohort Studies, Immunomodulating Agents, Crohn Disease, Immune-mediated inflammatory diseases, Hepatology, Gastroenterology, Humans, Tumor Necrosis Factor Inhibitors, Ustekinumab, Molecular targeted therapy, Combination therapy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUND: Use of a combination of targeted therapies (COMBIO) in patients with refractory/overlapping immune-mediated inflammatory diseases (IMIDs) has increased, but reported data remain scarce. We aimed to assess effectiveness and safety of COMBIO in patients with IMIDs. METHODS: We conducted a French ambispective multicenter cohort study from September 2020 to May 2021, including adults' patients with 1 or 2 IMIDs and treated at least 3-month with COMBIO. RESULTS: Overall, 143 patients were included. The most common IMIDs were Crohn's disease (63.6%), axial spondyloarthritis (37.7%), and ulcerative colitis (14%). Half of patients had only one IMID, of which 60% were Crohn's disease. Mean duration of COMBIO was 274.5±59.3 weeks, and COMBIO persistence at 104 weeks was estimated at 64.1%. The most frequent COMBIOs combined anti-TNF agents with vedolizumab (30%) or ustekinumab (28.7%). Overall, 50% of patients achieved significant and 27% mild-to-moderate improvement in patient-reported outcomes. Extended duration of COMBIO (aOR=1.09; 95% CI: 1.03-1.14; p=0.002) and diagnoses of two IMIDs (aOR=3.46; 95%CI: 1.29-9.26; p=0.013) were associated with significant improvement in patient-reported outcomes. Incidence of serious infection during COMBIO was 4.51 per 100 person-years (95% CI 2.20-8.27) and 5 COMBIOs were discontinued due to adverse events. CONCLUSIONS: COMBIO can be effective and safe in patients with refractory/overlapping IMIDs.
Published: 2023

5. Human papilloma virus‐16‐specific <scp>CD8</scp> + T‐cell expansions characterize different clinical forms of lichen planus and not lichen sclerosus et atrophicus

Author: Manuelle Viguier, Corine Pérals, Béatrice Poirier, Maxime Battistella, François Aubin, Hervé Bachelez, Jean‐Luc Prétet, Tarik Gheit, Massimo Tommasino, Antoine Touzé, Marie‐Lise Gougeon, Nicolas Fazilleau, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Genetic skin diseases : from disease mechanism to therapies (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence des Papillomavirus (CNRP), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), IRCCS Ist Tumori Giovanni Paolo II, Bari, Italy, Partenaires INRAE, Infectiologie et Santé Publique (UMR ISP), Université de Tours (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Regional Development Fund, Grant/Award Number: MP0022856, Institut National de la Sante et de la Recherche Medicale, Region Occitanie Pyrenees-Mediterranee, Grant/Award Number: #1901175, and Societe Francaise de Dermatologie et de Pathologie Sexuellement Transmissible
Subjects: T-cell, lichen planus, human papilloma virus, T-cell receptor, Dermatology, cytotoxic T lymphocytes, Molecular Biology, Biochemistry, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Lichen planus (LP) is a cutaneomucosal chronic inflammatory disease characterized by a CD8 + cytotoxic T-lymphocytes (CTL) infiltrate. In erosive oral LP, we found HPV16specific activated CTL in lesions, supporting a pathogenic contribution of HPV16. Here, we investigated whether a similar scenario occurs in other clinical forms of LP and in lichen sclerosus et atrophicus (LSA), another chronic disease also affecting the mucosa and/or the skin. Blood CTL from LP and LSA patients expressed significant higher levels of granzyme B, perforin and CD107a proteins than healthy donors. Expansions of TCRVß3 + CTL, with presence of TCR clonotypes identical to those previously detected in erosive oral LP, were found both in blood and mucosal/skin lesions of LP, and not of LSA patients. These expansions were enriched with HPV16-specific CD8 + T-cells as shown by their recognition of the E7 11-20 immunodominant epitope. In LSA patients, the peripheral repertoire of CTL was oligoclonal for TCRVß6 + CTL. Finally, although patients with LP and LSA have developed antibodies against HPV16
Published: 2023

6. Molecular characterization of Richter syndrome identifies de novo diffuse large B-cell lymphomas with poor prognosis

Author: Broséus, Julien, Hergalant, Sébastien, Vogt, Julia, Tausch, Eugen, Kreuz, Markus, Dartigeas, Caroline, Schneider, Christof, Mottok, Anja, Roos-Weil, Damien, Quinquenel, Anne, Moulin, Charline, Ott, German, Blanchet, Odile, Tomowiak, Cécile, Lazarian, Grégory, Rouyer, Pierre, Tournilhac, Olivier, Bernhart, Stephan H., Chteinberg, Emil, Gauchotte, Guillaume, Lomazzi, Sandra, Chapiro, Elise, Nguyen-Khac, Florence, Chery, Céline, Davi, Frédéric, Hunault, Mathilde, Houlgatte, Rémi, Rosenwald, Andreas, Delmer, Alain, Meyre, David, Béné, Marie-Christine, Thieblemont, Catherine, Lichter, Peter, Guéant, Jean-Louis, Guièze, Romain, Martin-Subero, José Ignacio, Ammerpohl, Ole, Cymbalista, Florence, Feugier, Pierre, Siebert, Reiner, Stilgenbauer, Stephan, Publica, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Universität Ulm - Ulm University [Ulm, Allemagne], Universitätsklinikum Ulm - University Hospital of Ulm, Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Fraunhofer (Fraunhofer-Gesellschaft), Service d'hématologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Service d'Hématologie Biologique [CHU Pitié-Salpêtrière], 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), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Service d'Hématologie [CHRU Nancy], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Robert-Bosch-Krankenhaus, Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology [Stuttgart], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service d'hématologie biologique [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Interdisciplinary Centre for Bioinformatics [Leipzig] (IZBI), Universität Leipzig [Leipzig], Service d’Hématologie Biologique [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Centre de Ressources Biologiques - [Nancy] (CRB Nancy), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Biochimie – Biologie moléculaire et Nutrition [CHRU Nancy], Service d'hématologie [Angers], PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institute of pathology [Würzburg], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-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), 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), Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany, Cancer Epigenetics Group, Cancer Epigenetics and Biology Program, Bellvitge Biomedical Research Institute, Barcelona, Spain, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), and Hergalant, Sébastien
Subjects: [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, Epigenomics, Chronic lymphocytic leukaemia, Lymphoma, B-Cell, B-Zell-Lymphom, biostatistics, General Physics and Astronomy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, General Biochemistry, Genetics and Molecular Biology, integrative genomics, DDC 570 / Life sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], ddc:570, ddc:610, Transcriptomics, Epigenetik, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Multidisciplinary, B-cell lymphoma, Gene Expression Profiling, Computational Biology, classifiers, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, bioinformatics, General Chemistry, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computational biology and bioinformatics, DLBCL, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Chronic lymphocytic leukemia, Epigenetics, Richter syndrome, DDC 610 / Medicine & health, CLL
Abstract: Richter syndrome (RS) is the transformation of chronic lymphocytic leukemia (CLL) into aggressive lymphoma, most commonly diffuse large B-cell lymphoma (DLBCL). We characterize 58 primary human RS samples by genome-wide DNA methylation and whole-transcriptome profiling. Our comprehensive approach determines RS DNA methylation profile and unravels a CLL epigenetic imprint, allowing CLL-RS clonal relationship assessment without the need of the initial CLL tumor DNA. DNA methylation- and transcriptomic-based classifiers were developed, and testing on landmark DLBCL datasets identifies a poor-prognosis, activated B-cell-like DLBCL subset in 111/1772 samples. The classification robustly identifies phenotypes very similar to RS with a specific genomic profile, accounting for 4.3-8.3% of de novo DLBCLs. In this work, RS multi-omics characterization determines oncogenic mechanisms, establishes a surrogate marker for CLL-RS clonal relationship, and provides a clinically relevant classifier for a subset of primary “RS-type DLBCL” with unfavorable prognosis., publishedVersion
Published: 2023

7. Cluster analysis unveils a severe persistent respiratory impairment phenotype 3-months after severe COVID-19

Author: Jeanne-Marie Perotin, Fabien Gierski, Lois Bolko, Sandra Dury, Sarah Barrière, Claire Launois, Maxime Dewolf, Stéphane Chouabe, Eric Bongrain, Davy Picard, Eric Tran, Yoann N’Guyen, Bruno Mourvillier, Amélie Servettaz, Amandine Rapin, Claude Marcus, François Lebargy, Arthur Kaladjian, Jean-Hugues Salmon, Gaetan Deslee, Service des maladies respiratoires et allergiques [CHU Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Cognition, Santé, Société (C2S), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), Université de Reims Champagne-Ardenne (URCA), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Centre Hospitalier de Charleville-Mezières, Centre Hospitalier Auban - Moët (Epernay, France), Hôpital de Châlons-en-Champagne, and dormoy, valerian
Subjects: Sarcopenia, Post-traumatic stress disorder, SARS-CoV-2, [SDV]Life Sciences [q-bio], COVID-19, Clustering, DLCO, [SDV] Life Sciences [q-bio], Phenotype, Quality of Life, Cluster Analysis, Humans, Prospective Studies, Respiratory Insufficiency
Abstract: Background The mid-term respiratory sequelae in survivors of severe COVID-19 appear highly heterogeneous. In addition, factors associated with respiratory sequelae are not known. In this monocentric prospective study, we performed a multidisciplinary assessment for respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. We analysed factors associated with severe persistent respiratory impairment, amongst demographic, COVID-19 severity, and 3-month assessment. Methods Patients with severe SARS-CoV-2 pneumonia requiring ≥ 4L/min were included for a systematic 3-month visit, including respiratory assessment (symptoms, lung function, CT scan), muscular evaluation (body composition, physical function and activity, disability), psychopathological evaluation (anxiety, depression, post-traumatic stress disorder-PTSD) and quality of life. A cluster analysis was performed to identify subgroups of patients based on objective functional measurements: DLCO, total lung capacity and 6-min walking distance (6MWD). Results Sixty-two patients were analysed, 39% had dyspnea on exercise (mMRC ≥ 2), 72% had DLCO LCO 48 ± 12%, 6MWD 299 ± 141 m). This SP cluster was characterized by older age, severe respiratory symptoms, but also sarcopenia/pre-sarcopenia, symptoms of PTSD and markedly impaired quality of life. It was not associated with initial COVID-19 severity or management. Conclusions and clinical implication We identified a phenotype of patients with severe persistent respiratory and muscular impairment and psychological distress 3 months after severe COVID-19. Our results highlight the need for multidisciplinary assessment and management after severe SARS-CoV-2 pneumonia. Trial registration The study was registered on ClinicalTrials.gov (May 6, 2020): NCT04376840
Published: 2022

8. Mild dyslipidemia accelerates tumorigenesis through expansion of Ly6Chi monocytes and differentiation to pro-angiogenic myeloid cells

Author: Thi Tran, Jean-Remi Lavillegrand, Cedric Lereverend, Bruno Esposito, Lucille Cartier, Melanie Montabord, Jaouen Tran-Rajau, Marc Diedisheim, Nadège Gruel, Khadija Ouguerram, Lea Paolini, Olivia Lenoir, Emmanuel Pinteaux, Eva Brabencova, Corinne Tanchot, Pauline Urquia, Jacqueline Lehmann-Che, Richard Le Naour, Yacine Merrouche, Christian Stockmann, Ziad Mallat, Alain Tedgui, Hafid Ait-Oufella, Eric Tartour, Stephane Potteaux, Tran, Thi [0000-0003-4012-5898], Lereverend, Cedric [0000-0002-9399-5638], Cartier, Lucille [0000-0003-0170-8396], Diedisheim, Marc [0000-0002-0418-1107], Lenoir, Olivia [0000-0001-8107-6987], Lehmann-Che, Jacqueline [0000-0001-6685-3354], Le Naour, Richard [0000-0003-1925-6041], Tedgui, Alain [0000-0002-7229-4875], Ait-Oufella, Hafid [0000-0002-2955-0183], Potteaux, Stephane [0000-0003-3068-8769], Apollo - University of Cambridge Repository, University of Zurich, Potteaux, Stephane, 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), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Institut Jean Godinot [Reims], UNICANCER, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), University of Manchester [Manchester], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Universität Zürich [Zürich] = University of Zurich (UZH), University of Cambridge [UK] (CAM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), ANR-11-INBS-0006,FLI,France Life Imaging(2011), Lenoir, Olivia, and Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID
Subjects: 10017 Institute of Anatomy, Carcinogenesis, General Physics and Astronomy, 610 Medicine & health, 1600 General Chemistry, 13/106, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Monocytes, General Biochemistry, Genetics and Molecular Biology, 14/1, 82/80, Mice, 1300 General Biochemistry, Genetics and Molecular Biology, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Tumor Microenvironment, 38/88, Animals, Myeloid Cells, 49/91, Dyslipidemias, Inflammation, 49/31, 1000 Multidisciplinary, Multidisciplinary, 82/16, article, 11401 Cancer Research Center (CRC), General Chemistry, 3100 General Physics and Astronomy, Mice, Inbred C57BL, Cell Transformation, Neoplastic, 692/4019/592/75/2099, 59/78, 570 Life sciences, biology, 64/60, 82/51, 631/67/327
Abstract: Funder: Association pour la recherche sur le cancer, Funder: Ligue Contre le Cancer, Cancer and cardiovascular disease (CVD) share common risk factors such as dyslipidemia, obesity and inflammation. However, the role of pro-atherogenic environment and its associated low-grade inflammation in tumor progression remains underexplored. Here we show that feeding C57BL/6J mice with a non-obesogenic high fat high cholesterol diet (HFHCD) for two weeks to induce mild dyslipidemia, increases the pool of circulating Ly6Chi monocytes available for initial melanoma development, in an IL-1β-dependent manner. Descendants of circulating myeloid cells, which accumulate in the tumor microenvironment of mice under HFHCD, heighten pro-angiogenic and immunosuppressive activities locally. Limiting myeloid cell accumulation or targeting VEGF-A production by myeloid cells decrease HFHCD-induced tumor growth acceleration. Reverting the HFHCD to a chow diet at the time of tumor implantation protects against tumor growth. Together, these data shed light on cross-disease communication between cardiovascular pathologies and cancer.
Published: 2022
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9. Impact of Childhood Onset Psoriasis on Addictive Behaviours, Socioeconomic and Educational Data in Adulthood

Author: Emmanuel, Mahé, Florence, Tubach, Denis, Jullien, Diep, Tran, Carle, Paul, Marie, Beylot-Barry, Alain, Dupuy, Manuelle, Viguier, Marie-Aleth, Richard, Emilie, Sbidian, Nathalie, Beneton, Pascal, Joly, Olivier, Chosidow, Hervé, Bachelez, Centre Hospitalier Victor Dupouy, Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Hospices Civils de Lyon (HCL), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), 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), Bordeaux Research In Translational Oncology [Bordeaux] (BaRITOn), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), CHU Marseille, Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Le Mans (CH Le Mans), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), French Ministry of Health [PHRC AOM 09 195], French Drugs Agency (ANSM), AbbVie, Janssen, MSD France, Pfizer, Departement a la Recherche Clinique et au Developpement (DRCD), Assistance Publique-Hopitaux de Paris, French Society of Dermatology (Societe Francaise de Dermatologie), Groupe de Recherche sur le Psoriasis, Jonchère, Laurent, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Adult, socioeconomic data, alcohol, [SDV]Life Sciences [q-bio], Dermatology, General Medicine, psoriasis, tobacco, Behavior, Addictive, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, educational level, Socioeconomic Factors, children, adolescent, Educational Status, Humans, Prospective Studies, Child
Abstract: International audience; Paediatric psoriasis has been associated with school absenteeism, limitation of physical activities, psychiatric disorders and, in the longer term, with sexual dysfunction and addictions. This raises the hypothesis that childhood onset psoriasis may affect patients' educational development, and further social and professional outcomes. This study evaluated the relationship between childhood onset psoriasis and patients' educational and socioeconomic characteristics, and the development of addictions in adulthood. This cross-sectional ancillary study captured patients' characteristics at baseline in the French PSOBIOTEQ registry. Data in adulthood included: educational (baccalaureate) and socioeconomic (working activity) groups, smoking status (self-reporting of being a current smoker vs past smoker or non-smoker), alcohol consumption (defined as at least 1 glass of alcoholic beverage per day), and living conditions (alone/family/social institutions; child at home). A total of 1,960 patients were included, of whom 26.2% had childhood onset psoriasis. In multivariate analyses, childhood onset psoriasis was associated with smoker status (p = 0.02). No association was observed with educational level, working activity, living conditions, or alcohol consumption. This study provides reassuring data overall with regard to the impact of childhood onset psoriasis on major social outcomes. Evidence for some association with addictive behaviours paves the way for larger prospective studies assessing in depth the social and educational impact of this disease.
Published: 2022

10. Effectiveness and tolerance of Janus kinase inhibitors for the treatment of recalcitrant atopic dermatitis in a real-life French multicenter adult cohort

Author: Julia Vanlerberghe, Frédéric Dezoteux, Claire Martin, Marie Jachiet, Angèle Soria, Florence Tétart, Anne-Bénédicte Modeste-Duval, Anne-Claire Bursztejn, Laurent Misery, François Aubin, Audrey Lasek, Camille Leleu, Aurélie Du-Thanh, Justine Pasteur, Pauline Pralong, Audrey Nosbaum, Catherine Droitcourt, Manuelle Viguier, Marie Tauber, Julien Seneschal, Sébastien Barbarot, Delphine Staumont-Sallé, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Protéines de défense des réponses immune et inflammatoire : identification, régulation et rôles physiopathologiques, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nancy (CHU Nancy), Hopital de Bohars - CHRU Brest (CHU - BREST ), Department of Dermatology (CHU Besançon), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université de Clermont-Ferrand, Université Grenoble Alpes (UGA), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Physiopathologie des Adaptations Nutritionnelles (PhAN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, and Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)
Subjects: Dermatology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience
Published: 2022

11. Users of biologics in clinical practice: would they be eligible for phase III clinical studies? Cohort Study in the French Psoriasis Registry PSOBIOTEQ

Author: M. Masson Regnault, Denis Jullien, Pascal Joly, J. Castañeda‐Sanabria, Emilie Sbidian, M. Viguier, Alain Dupuy, Hervé Bachelez, M.H.T. Diep Tran, Olivier Chosidow, E. Mahé, Nathalie Beneton, Carle Paul, Marie Beylot-Barry, Florence Tubach, Marie Aleth Richard, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, Brodalumab, Dermatology, law.invention, Cohort Studies, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Psoriasis, Internal medicine, Ustekinumab, medicine, Humans, Registries, Adverse effect, ComputingMilieux_MISCELLANEOUS, Aged, Aged, 80 and over, Biological Products, business.industry, Middle Aged, medicine.disease, 3. Good health, Clinical trial, Infectious Diseases, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, Inclusion and exclusion criteria, Female, Dermatologic Agents, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Cohort study, medicine.drug
Abstract: Background Numerous inclusion and exclusion criteria are involved in phase III moderate to severe psoriasis trials investigating the safety and efficacy of biologics. This questions the generalization of results. Methods In this cohort study, we applied inclusion/exclusion criteria for phase III trials from original protocols (adalimumab - REVEAL, ustekinumab - PHOENIX, brodalumab - AMAGINE, secukinumab FIXTURE) to all patients enrolled in the PsoBioTeq prospective registry who received a biological agent for the first time between July 2012 and November 2017. We then compared the efficacy, drug survival and occurrence of adverse events between patients who satisfied/did not satisfy the eligibility criteria for these phase III trials. Results A total of 1267 patients were enrolled, of whom 993 (78.4%) were not eligible for at least one RCT (randomized controlled trial) and 251 (19.1%) did not meet the PASI/PGA severity requirements. Apart from disease severity, the most frequent criteria resulting in exclusion were as follows: non-plaque psoriasis (12.6%), significant cardiac disease (8.4%), significant liver disease (7.3%), elevated liver enzymes (4.9-9.6%) and personal history of diabetes (9.2%). There was no difference in drug survival between the two groups. The incidence ratio of adverse events was significantly lower in eligible versus non-eligible patients [0.78 (95% CI 0.62-0.97) (P = 0.03)]. Conclusion The majority of patients treated with biologics in the PsoBioTeq real-life registry would not have been eligible for phase III moderate to severe psoriasis trials. Patients not eligible for psoriasis phase III clinical trials have a higher incidence of adverse events.
Published: 2019

12. Health-Related Quality of Life in Adults with Cystic Fibrosis: Familial, Occupational, Social, and Mental Health Predictors

Author: Julien Ancel, Claire Launois, Jeanne-Marie Perotin, Bruno Ravoninjatovo, Pauline Mulette, Jean Hagenburg, Julie Malet, Muriel Griffon, Sophie Carré, François Lebargy, Gaëtan Deslée, Sandra Dury, Service des maladies respiratoires et allergiques [CHU Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), and dormoy, valerian
Subjects: [SDV] Life Sciences [q-bio], Health Information Management, Leadership and Management, [SDV]Life Sciences [q-bio], cystic fibrosis, quality of life, anxiety, depression, CFQ-R, Health Policy, Health Informatics
Abstract: International audience; Background: Cystic Fibrosis (CF) adult patients experience daily physical symptoms and disabilities that may impact their quality of life and mental health. Methods: This prospective study aimed to evaluate the relative contribution of the familial, occupational, and social environment, besides that of the main physical and mental health factors, to the quality of life of CF adult patients using the Cystic Fibrosis Questionnaire-Revised (CFQ-R) in a multivariate model. Results: Fifty patients were analyzed (70% of men; median age of 25 years; median body mass index of 21 kg/m²; median FEV1 of 57%). Anxiety and depression scores were negatively associated with 9 of the 12 CFQ-R domains. When controlling for anxiety and depression, FEV1% and BMI were significant positive predictors of several domains of the CFQ-R. All the familial, occupational, and social components analyzed but one (professional training) were predictors of at least one domain of the CFQ-R. Conclusion: Anxiety and depression explained a greater proportion of the variance than physical variables (age, sex, BMI, FEV1%, and exacerbation in the last year) in CF HRQoL. Many familial, occupational, and social components were also specifically and independently predictors of some HRQoL domains. Their screening might help identifying CF patients eligible for specific interventions, focusing on the impaired QoL dimensions.
Published: 2022

13. Large International Validation of ABSIS and PDAI Pemphigus Severity Scores

Author: Hébert, Vivien, Boulard, Claire, Houivet, Estelle, Lehembre, Sophie, Borradori, Luca, Della, Rocco, Feliciani, Claudio, Fania, Luca, Zambruno, Giovanna, Camaioni, Diana, Didona, Biago, Marinovic, Branka, Schmidt, Enno, Schumacher, Nina, Hü Nefeld 10, Christian, Schanz, Stefan, Kern, Johannes, Hofmann, Silke, Bouyeure, Anne, Picard-Dahan, Catherine, Prost-Squarcioni, Catherine, Caux, Frederic, Alexandre, Marina, Ingen-Housz-Oro, Saskia, Bagot, Martine, Tancrede-Bohin, Emmanuelle, David Bouaziz, Jean, Franck, Nathalie, Vabres, Pierre, Labeille, Bruno, Richard, Marie, Delaporte, Emmanuel, Dupuy, Alain, D'Incan, Michel, Quereux, Gaelle, Skowro, François, Paul, Carle, Livideanu, Cristina, Beylot-Barry, Marie, Doutre, Marie, Avenel-Audran, Martine, Bedane, Christophe, Bernard, Philippe, Machet, Laurent, Maillard, Hervé, Jullien, Denis, Debarbieux, Sebastien, Sassolas, Bruno, Misery, Laurent, Abasq, Claire, Dereure, Olivier, Lagoutte, Philippe, Ferranti, Vincent, Werth, Victoria, Murrell, Dedee, Hertl, Michael, Benichou, Jacques, Joly, Pascal, Duvert Lehembre, Sophie, Della Torre, Rocco, Hünefeld, Christian, Kern, Johannes Steffen, Bouyeure, Anne Charlotte, Bouaziz, Jean David, Richard, Marie Aleth, D’Incan, Michel, Livideanu, Cristina Bulai, Doutre, Marie Sylvie, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Pharmacoepidemiologie et évaluation de l'impact des produits de santé sur les populations, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Universität Bern [Bern], Molecular and Cell Biology Laboratory, IDI-IRCCS, Rome, Service de Dermatologie, Hôpital Bichat, AP-HP, Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de dermatologie [Avicenne], Hôpital Avicenne-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13), CHU Henri Mondor, Service de Dermatologie [AP-HP Hôpital Saint Louis, Paris], Université Paris Diderot - Paris 7 (UPD7)-AP-HP Hôpital Saint-Louis, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University Hospital of St-Etienne, Department of Dermatology, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes (UGA), Service de dermatologie (CHRU de Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Dermatologie [Rennes], CHU Pontchaillou [Rennes], Imagerie Moléculaire et Stratégies Théranostiques - Clermont Auvergne (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Département de Dermatologie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Dermatologie [CHU Limoges], CHU Limoges, Club Rhumatismes et Inflammation, Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Génétique médicale et fonctionnelle du cancer et des maladies neuropsychiatriques, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Seventh Framework Programme, French Society of Dermatology, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), CHU Rouen, Normandie Université (NU), Service de dermatologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Unité de biostatistiques [Rouen], Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 (UPD7), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), L'Oréal recherche et innovation, L'Oréal, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie, Hôtel-Dieu, Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Toulouse III - Paul Sabatier (UPS), Immunodermatologie, Cytokines, Cancer - EA 7319 (ICA), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), INSERM U1234, Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Hopital Saint-Louis [AP-HP] (AP-HP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de Dermatologie [Rennes] = Dermatology [Rennes], Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Université Bordeaux Segalen - Bordeaux 2-Université de Rouen Normandie (UNIROUEN), Universität Bern [Bern] (UNIBE), IDI-IRCCS [Roma, Italy], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], CHU Henri Mondor [Créteil], Service de Dermatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Université de Toulouse (UT), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Autoimmune Bullous Skin Disorder Intensity Score, Intraclass correlation, [SDV]Life Sciences [q-bio], intraclass correlation coefficient, Autoimmunity, PV, Validation Studies as Topic, Severity of Illness Index, Biochemistry, PDAI, 0302 clinical medicine, Medicine, DLQI, Pemphigus foliaceus, Skin, integumentary system, Desmoglein 1, PGA, CI, 3. Good health, ABSIS, month, 030220 oncology & carcinogenesis, PF, medicine.medical_specialty, pemphigus vulgaris, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, 03 medical and health sciences, Dermatology Quality of Life Index, Internal medicine, Severity of illness, Humans, In patient, pemphigus foliaceus, Molecular Biology, Autoantibodies, Pemphigus severity scores, ICC, business.industry, Pemphigus vulgaris, Cell Biology, medicine.disease, Confidence interval, Moderate extent, Pemphigus Disease Area Index, Pemphigus, 030104 developmental biology, confidence interval, Physician Global Assessment, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IF 6.448 (2017); International audience; The Pemphigus Disease Area Index (PDAI) and Autoimmune Bullous Skin Disorder Intensity-Score (ABSIS) scores have been proposed to provide an objective measure of pemphigus activity. These scores have been evaluated only on already treated patients mainly with mild to moderate activity. The objective was to assess the interrater reliability of ABSIS and PDAI scores and their correlation with other severity markers in a large international study. Consecutive patients with newly diagnosed pemphigus were enrolled in 31 centers. Severity scores were recorded during a 24-month period by the same two blinded investigators. Serum was collected at each visit for ELISA measurement of anti-desmoglein antibodies. The intraclass correlation coefficient (ICC) and Spearman rank correlation coefficient were calculated. A total of 116 patients with pemphigus vulgaris (n = 84) or pemphigus foliaceus (n = 32) were included. At baseline, the ABSIS and PDAI ICCs were 0.90 (95% confidence interval [CI] = 0.85-0.93), and 0.91(95% CI = 0.87-0.94), respectively. The ICCs for PDAI were higher in moderate and extensive pemphigus (ICC = 0.82, 95% CI = 0.63-0.92 and ICC = 0.80, 95% CI = 0.62-0.90, respectively) than in patients with intermediate (significant) extent (ICC = 0.50, 95% CI = 0.27-0.68). Conversely, the ICCs for ABSIS were lower in patients with moderate extent (ICC = 0.44, 95% CI = 0.004-0.74) than in those with intermediate or extensive forms, (ICC = 0.69, 95% CI = 0.51-0.81 and ICC = 0.75, 95% CI = 0.51-0.88, respectively). During patients' follow-up, the ICCs of both ABSIS and PDAI scores remained higher than 0.70. ABSIS and PDAI skin (r = 0.71 and r = 0.75) but not mucosal (r = 0.32 and r = 0.37) subscores were correlated with the evolution of anti-DSG1 and anti-DSG3 ELISA values, respectively. ABSIS and PDAI scores are robust tools to accurately assess pemphigus activity.
Published: 2019

14. Low-Dose IL-2 for Treating Moderate to Severe Alopecia Areata: A 52-Week Multicenter Prospective Placebo-Controlled Study Assessing its Impact on T Regulatory Cell and NK Cell Populations

Author: Michel Ticchioni, Jean-David Bouaziz, Jean-Philippe Lacour, Pascal Reygagne, Marie-Aleth Richard, Sandrine Monestier, Florence Le Duff, Henri Montaudié, Thierry Passeron, Olivier Dereure, Manuelle Viguier, Eric Fontas, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Assistance Publique - Hôpitaux de Marseille (APHM), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), and 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)
Subjects: Moderate to severe, medicine.medical_specialty, Cell, Placebo-controlled study, Dermatology, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, T-regulatory cell, Internal medicine, medicine, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Low dose, Cell Biology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Alopecia areata, medicine.disease, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience
Published: 2021

15. Pre‐exposure prophylaxis for HIV infection and new sexually transmitted infections among men who have sex with men: real‐life experience from three sexual health clinics in France

Author: Anne Raphaelle Schmidt‐Guerre, Fabien Pelletier, C. Vanhaecke, Isabelle Ginet‐Mermet, François Aubin, Dorothéeorothée Lambert, Morgane Colas, Thomashomas Lihoreau, Manuelle Viguier, Catherine Courtieu, Catherine Merle, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: Male, medicine.medical_specialty, Sexual Behavior, Human immunodeficiency virus (HIV), Sexually Transmitted Diseases, HIV Infections, Dermatology, medicine.disease_cause, Men who have sex with men, 03 medical and health sciences, Pre-exposure prophylaxis, Sexual and Gender Minorities, 0302 clinical medicine, medicine, Humans, 030212 general & internal medicine, Homosexuality, Male, ComputingMilieux_MISCELLANEOUS, Reproductive health, 0303 health sciences, 030306 microbiology, business.industry, 3. Good health, Infectious Diseases, Family medicine, Pre-Exposure Prophylaxis, France, Sexual Health, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2021

16. Absence of Anti-Glomerular Basement Membrane Antibodies in 200 Patients With Systemic Lupus Erythematosus With or Without Lupus Nephritis: Results of the GOODLUPUS Study

Author: Bernard Bonnotte, P. Orquevaux, Bach Nga Pham, Zahir Amoura, S. Revuz, Delphine Giusti, Laurent Arnaud, Moustapha Dramé, Gilles Blaison, Marcelle Tonye Libyh, Thierry Martin, Hanns-Martin Lorenz, Nadine Magy-Bertrand, Grace Stockton-Bliard, Reinhard E. Voll, Amélie Servettaz, Grégory Gatouillat, Jan Chrusciel, Nellie Bourse Chalvon, Jean-Loup Pennaforte, Andreas Schwarting, Thierry Tabary, Oliver Hinschberger, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: Male, Anti-Glomerular Basement Membrane Disease, [SDV]Life Sciences [q-bio], Lupus nephritis, Aucun, urologic and male genital diseases, Severity of Illness Index, Gastroenterology, anti-glomerular basement membrane antibodies, 0302 clinical medicine, systemic lupus erythematosus, Lupus Erythematosus, Systemic, Immunology and Allergy, 030212 general & internal medicine, Original Research, medicine.diagnostic_test, biology, anti-GBM glomerulonephritis, Glomerular basement membrane, IIf, Middle Aged, 3. Good health, Titer, medicine.anatomical_structure, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, Vasculitis, Adult, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Immunology, 03 medical and health sciences, Antigen, Internal medicine, anti-GBM antibodies, medicine, Humans, Autoantibodies, Retrospective Studies, 030203 arthritis & rheumatology, lupus nephritis, business.industry, Goodpasture disease, medicine.disease, Case-Control Studies, Immunoassay, biology.protein, business, lcsh:RC581-607, Biomarkers
Abstract: IntroductionAnti-glomerular basement membrane (GBM) antibodies are pathogenic antibodies first detected in renal-limited anti-GBM disease and in Goodpasture disease, the latter characterized by rapidly progressive crescentic glomerulonephritis combined with intra-alveolar hemorrhage. Studies have suggested that anti-GBM antibody positivity may be of interest in lupus nephritis (LN). Moreover, severe anti-GBM vasculitis cases in patients with systemic lupus erythematosus (SLE) have been described in the literature, but few studies have assessed the incidence of anti-GBM antibodies in SLE patients.ObjectiveThe main study objective was to determine if positive anti-GBM antibodies were present in the serum of SLE patients with or withoutproliferativerenal damage and compared to a healthy control group.MethodologyThis retrospective study was performed on SLE patients’ sera from a Franco-German European biobank, developed between 2011 and 2014, from 17 hospital centers in the Haut-Rhin region. Patients were selected according to their renal involvement, and matched by age and gender. The serum from healthy voluntary blood donors was also tested. Anti-GBM were screened by fluorescence enzyme immunoassay (FEIA), and then by indirect immunofluorescence (IIF) in case of low reactivity detection (titer >6 U/ml).ResultsThe cohort was composed of 100 SLE patients withproliferativeLN (27% with class III, 67% with class IV, and 6% with class V), compared to 100 SLE patients without LN and 100 controls. Patients were mostly Caucasian and met the ACR 1997 criteria and/or the SLICC 2012 criteria. Among the 300 tested sera, no significant levels of anti-GBM antibodies were detected (>10 U/ml) by the automated technique, three sera were found “ambivalent” (>7 U/ml): one in the SLE with LN group and two in the SLE without LN group. Subsequent IIF assays did not detect anti-GBM antibodies.ConclusionAnti-GBM antibodies were not detected in the serum of Caucasian patients with SLE, even in case of renal involvement, a situation favoring the antigenic exposure of glomerular basement membranes. Our results reaffirm the central role of anti-GBM antibodies as a specific diagnostic biomarker for Goodpasture vasculitis and therefore confirm that anti-GBM antibody must not be carried out in patients with SLE (with or without LN) in the absence of disease-suggestive symptoms.
Published: 2020

17. Anti-Jo1 Antibody Quantification Serve as a Prognostic Factor in Antisynthetase Syndrom

Author: Bolko, Loïs, Didier, Kevin, Salmon, Jean-Hugues, Miyara, Makoto, Toquet, Segolene, Servettaz, Amelie, Allenbach, Yves, Benveniste, Olivier, Hervier, Baptiste, 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), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Hôpital Maison Blanche, Centre Hospitalier Universitaire de Reims (CHU Reims), Centre d'Immunologie et des Maladies Infectieuses (CIMI), 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), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Centre de recherche en Myologie – U974 SU-INSERM, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: [SDV]Life Sciences [q-bio]
Abstract: International audience
Published: 2020

18. Impact of the French guidelines on the prescribing habits of systemic treatments for moderate‐to‐severe psoriasis

Author: Marie Beylot-Barry, Axel Patrice Villani, M. Viguier, Bernard Guillot, Denis Jullien, Florent Amatore, Marie Tauber, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: medicine.medical_specialty, business.industry, Moderate to severe psoriasis, MEDLINE, Antibodies, Monoclonal, Dermatology, medicine.disease, 3. Good health, Biologic Agents, Habits, Infectious Diseases, Psoriasis, medicine, Humans, business, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2020

19. Efficacy and safety of TNF blockers and of ustekinumab in palmoplantar pustulosis and in acrodermatitis continua of Hallopeau

Author: Denis Jullien, Marie Aleth Richard, Julien Seneschal, F. Aubin, S. Hegazy, Michel D'Incan, E. Mahé, Coralie Barbe, Céline Girard, B. Husson, Emilie Brenaut, Hervé Bachelez, Curdin Conrad, Emilie Sbidian, M. Viguier, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Service de Dermatologie et pathologies vasculaires [CH Argenteuil], Centre Hospitalier Victor Dupouy, Institut Laue-Langevin (ILL), ILL, Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de dermatologie, Hôpital Augustin Morvan-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de biologie cellulaire et moléculaire, Institut National de la Recherche Agronomique (INRA), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Robert Debré, CRCM, Université Paris7, Assistance Publique - Hôpitaux de Paris, Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Male, medicine.medical_specialty, Palmoplantar pustulosis, [SDV]Life Sciences [q-bio], education, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Gastroenterology, Etanercept, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Psoriasis, Internal medicine, Ustekinumab, parasitic diseases, Adalimumab, medicine, otorhinolaryngologic diseases, Humans, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, business.industry, Acrodermatitis, Odds ratio, medicine.disease, Infliximab, 3. Good health, Infectious Diseases, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor Necrosis Factor Inhibitors, business, medicine.drug
Abstract: Background Palmoplantar pustulosis (PPP) and acrodermatitis continua of Hallopeau (ACH) are rare variants of psoriasis. Knowledge of the efficacy of biologics is scarce. Objectives To evaluate the real-life efficacy of tumour necrosis factor blockers and ustekinumab in PPP and in ACH. Methods A multicentre retrospective descriptive study was conducted in 19 dermatology departments, including all patients with PPP or ACH seen from 2014 to 2016 who received one of the studied biologics. The data were collected by a standardized document. Factors associated with complete clearance (CC) were analysed by multivariate analysis, estimating odds ratios (ORs) and 95% confidence intervals (CIs). Results Among 92 patients included, 50 received adalimumab, 44 ustekinumab, 36 etanercept and 31 infliximab. Improvement and CC were observed in 83.9% and 20.0% patients receiving infliximab, 75.0% and 38.6% ustekinumab, 57.1% and 20.0% etanercept and 60.4% and 29.2% adalimumab. We found no significant difference in CC rates or duration of treatment among the biological treatments (P = 0.18 and P = 0.10, respectively). On multivariate analysis, CC with etanercept was associated with the ACH form and not smoking [OR = 9.5 (95% CI 1.1-82.7), P = 0.04 and 0.1 (0.01-0.9), P = 0.04]; with ustekinumab, male sex and absence of obesity [6.0 (1.3-28.6), P = 0.02 and 4.7 (1.0-22.7), P = 0.05]; with adalimumab, the ACH form [11.9 (2.7-52.3), P = 0.001]; and with infliximab, obesity [5.6 (1.1-29.4), P = 0.04]. Conclusions We found no difference in efficacy between TNF blockers and ustekinumab and among the three different TNF blockers in real life for PPP or ACH, which reveals the heterogeneity of clinical response to biologics in pustular psoriasis as compared with plaque psoriasis.
Published: 2020

20. Corticosteroid therapy for patients with COVID-19 pneumonia: a before–after study

Author: Madeline Pascard, M. Hentzien, Lukshe Kanagaratnam, Firouzé Bani-Sadr, Yohan Nguyen, Laurent Andreoletti, Damien Jolly, Amélie Servettaz, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Laboratoire de Virologie Médicale et Moléculaire - EA 4684 (CardioVir), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: 0301 basic medicine, Male, Multivariate analysis, [SDV]Life Sciences [q-bio], law.invention, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Adrenal Cortex Hormones, Corticosteroid, Pharmacology (medical), 030212 general & internal medicine, Hospital Mortality, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Hazard ratio, General Medicine, Early warning score, Intensive care unit, 3. Good health, Infectious Diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Coronavirus Infections, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Pneumonia, Viral, Lower risk, Article, 03 medical and health sciences, Betacoronavirus, Internal medicine, medicine, Humans, COVID-19 pneumonia, Pandemics, Aged, business.industry, SARS-CoV-2, COVID-19, medicine.disease, Confidence interval, respiratory tract diseases, COVID-19 Drug Treatment, Pneumonia, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Highlights • Severe COVID-19 patients present overwhelming inflammatory reactions leading to lung injury. • Corticosteroids may beneficially modulate the host immune response to COVID-19 pneumonia. • Before–after study evaluating the effect of corticosteroid addition to COVID-19 pneumonia treatment on hospital mortality. • In multivariate analysis, the ‘after’ period was associated with an adjusted lower risk of death (aHR = 0.47; P = 0.04). • ‘After’ period was also associated with lower risk of ICU admission or death before ICU admission (aHR = 0.37; P < 0.001)., Anti-inflammatory drugs such as corticosteroids may beneficially modulate the host inflammatory response to coronavirus disease 2019 (COVID-19) pneumonia. The aim of this study was to evaluate the impact of addition of corticosteroids to the hospital protocol for treatment of suspected or confirmed COVID-19 pneumonia on rates of death or intensive care unit (ICU) admission. A before–after study was performed to evaluate the effect of addition of corticosteroids to our institution's COVID-19 treatment protocol on hospital mortality. A total of 257 patients with a COVID-19 diagnosis were included in this study between 3 March 2020 and 14 April 2020. As corticosteroids were widely used after 27 March 2020, two periods were considered for the purposes of this study: the ‘before’ period from 3–20 March 2020 (n = 85); and the ‘after’ period from 26 March–14 April 2020 (n = 172). The ‘after’ period was associated with a lower risk of death [adjusted hazard ratio (aHR) = 0.47, 95% confidence interval (CI) 0.23–0.97; P = 0.04] and a lower risk of ICU admission or of death before ICU admission (aHR = 0.37, 95% CI 0.21–0.64; P = 0.0005) by multivariate analysis adjusted for age, National Early Warning score and institutionalisation status. In conclusion, addition of corticosteroids to our institution's COVID-19 treatment protocol was associated with a significant reduction in hospital mortality in the ‘after’ period.
Published: 2020

21. Acute severe idiopathic lymphoid interstitial pneumonia

Author: Olivier Passouant, Maxime Dewolf, Sebastian Sandu, Antoine Dumazet, Anne Durlach, Youssef Lamkouan, Sandra Dury, François Lebargy, C. Launois, Gaëtan Deslée, Remi Picot, Jeanne-Marie Perotin, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: medicine.medical_specialty, Pleural effusion, [SDV]Life Sciences [q-bio], lymphoid, Lung biopsy, Gastroenterology, Hypoxemia, 03 medical and health sciences, Antineoplastic Agents, Immunological, Fatal Outcome, 0302 clinical medicine, rituximab, lymphoproliferative, Internal medicine, Humans, Medicine, Lymphoid interstitial pneumonia, 030212 general & internal medicine, Clinical Case Report, Lung, Immunodeficiency, Aged, interstitial lung disease, Past medical history, medicine.diagnostic_test, business.industry, General Medicine, medicine.disease, 3. Good health, respiratory tract diseases, Bronchoalveolar lavage, 030220 oncology & carcinogenesis, Female, Rituximab, medicine.symptom, Lung Diseases, Interstitial, Tomography, X-Ray Computed, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug, Research Article
Abstract: International audience; Rationale: Lymphoid interstitial pneumonia is a rare benign pulmonary lymphoproliferative disorder usually presenting with a subacute or chronic condition and frequently associated with autoimmune disorders, dysgammaglobulinemia, or infections. Patient concerns: A 74-year-old woman with no past medical history presented with acute dyspnea, nonproductive cough, hypoxemia (room air PaO 2 : 48 mmHg) and bilateral alveolar infiltrates with pleural effusion. Antibiotics and diuretics treatments did not induce any improvement. No underlying condition including cardiac insufficiency, autoimmune diseases, immunodeficiency, or infections was found after an extensive evaluation. Bronchoalveolar lavage revealed a lymphocytosis (60%) with negative microbiological findings. High-dose intravenous corticosteroids induced a mild clinical improvement only, which led to perform a surgical lung biopsy revealing a lymphoid interstitial pneumonia with no sign of lymphoma or malignancies. Diagnoses: Acute severe idiopathic lymphoid interstitial pneumonia. Interventions: Ten days after the surgical lung biopsy, the patient experienced a dramatic worsening leading to invasive mechanical ventilation. Antibiotics and a new course of high-dose intravenous corticosteroids did not induce any improvement, leading to the use of rituximab which was associated with a dramatic clinical and radiological improvement allowing weaning from mechanical ventilation after 10 days. Outcomes: Despite the initial response to rituximab, the patient exhibited poor general state and subsequent progressive worsening of respiratory symptoms leading to consider symptomatic palliative treatments. The patient died 4 months after the diagnosis of lymphoid interstitial pneumonia. Lessons: Idiopathic lymphoid interstitial pneumonia may present as an acute severe respiratory insufficiency with a potential transient response to rituximab. Abbreviations: EBV = Epstein-Barr virus, HIV = human immunodeficiency virus, HTLV-1 = human T-cell lymphotropic virus-1, LIP = lymphoid interstitial pneumonia.
Published: 2020

22. Different phenotypes in dermatomyositis associated with anti-MDA5 antibody

Author: Allenbach, Yves, Uzunhan, Yurdagul, Toquet, Ségolène, Leroux, Gaëlle, Gallay, Laure, Marquet, Alicia, Meyer, Alain, Guillaud, Constance, Limal, Nicolas, Gagnadoux, Frédéric, Hervier, Baptiste, Borie, Raphaël, Deligny, Christophe, Terrier, Benjamin, Berezne, Alice, Audia, Sylvain, Champtiaux, Nicolas, Devilliers, Hervé, Voermans, Nicol, Diot, Elizabeth, Servettaz, Amélie, Marhadour, Thierry, Castelain, Vincent, Humbert, Sébastien, Blanchard-Delaunay, Claire, Tieulie, Nathalie, Charles, Pierre, Gerin, Magdalena, Mekinian, Arsène, Priou, Pascaline, Meurice, Jean Claude, Tazi, Abdellatif, Cottin, Vincent, Miyara, Makoto, Grange, Benjamin, Israël-Biet, Dominique, Phin-Huynh, Sophie, Bron, Camille, De Saint Martin, Luc, Fabien, Nicole, Mariampillai, Kubéraka, Nunes, Hilario, Benveniste, Olivier, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: [SDV]Life Sciences [q-bio], [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract: International audience; Objectives The predominance of extramuscular manifestations (e.g., skin rash, arthralgia, interstitial lung disease [ILD]) as well as the low frequency of muscle signs in anti–melanoma differentiation-associated gene 5 antibody–positive (anti-MDA5+) dermatomyositis caused us to question the term myositis-specific antibody for the anti-MDA5 antibody, as well as the homogeneity of the disease. Methods To characterize the anti-MDA5+ phenotype, an unsupervised analysis was performed on anti-MDA5+ patients (n = 83/121) and compared to a group of patients with myositis without anti-MDA5 antibody (anti-MDA5−; n = 190/201) based on selected variables, collected retrospectively, without any missing data. Results Within anti-MDA5+ patients (n = 83), 3 subgroups were identified. One group (18.1%) corresponded to patients with a rapidly progressive ILD (93.3%; p < 0.0001 across all) and a very high mortality rate. The second subgroup (55.4%) corresponded to patients with pure dermato-rheumatologic symptoms (arthralgia; 82.6%; p < 0.01) and a good prognosis. The third corresponded to patients, mainly male (72.7%; p < 0.0001), with severe skin vasculopathy, frequent signs of myositis (proximal weakness: 68.2%; p < 0.0001), and an intermediate prognosis. Raynaud phenomenon, arthralgia/arthritis, and sex permit the cluster appurtenance (83.3% correct estimation). Nevertheless, an unsupervised analysis confirmed that anti-MDA5 antibody delineates an independent group of patients (e.g., dermatomyositis skin rash, skin ulcers, calcinosis, mechanic's hands, ILD, arthralgia/arthritis, and high mortality rate) distinct from anti-MDA5− patients with myositis. Conclusion Anti-MDA5+ patients have a systemic syndrome distinct from other patients with myositis. Three subgroups with different prognosis exist.
Published: 2020

23. Neutrophil Extracellular Traps Generation Relates with Early Stage and Vascular Complications in Systemic Sclerosis

Author: Didier, Kevin, Giusti, Delphine, Le Jan, Sebastien, Terryn, Christine, Muller, Celine, Pham, Bach Nga, Le Naour, Richard, Antonicelli, Frank, Servettaz, Amelie, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Plateforme en Imagerie Cellulaire et Tissulaire (PICT), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)
Subjects: NET, integumentary system, systemic sclerosis, lcsh:R, neutrophil extracellular traps, [SDV.IMM]Life Sciences [q-bio]/Immunology, NETosis, lcsh:Medicine, scleroderma, skin and connective tissue diseases, PMN, Article, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Systemic sclerosis (SSc) is a systemic disease characterized by a great clinical and immunological heterogeneity whose pathophysiology is still being unraveled. Recently, innate immunity has been proposed to participate to the pathogenesis of SSc. In this study, we investigated the release of neutrophil extracellular traps (NETs) according to patient phenotype. Polymorphonuclear neutrophils (PMN) from 34 SSc patients and 26 healthy controls were stimulated by serum from SSc or healthy subject. NETs were visualized using epifluorescence microscope after DNA, myeloperoxidase, and Histone H3 tagging. Area of NETs were quantified using an original macro running in ImageJ&reg, software. PMN from SSc patients were significantly more prone to releasing NETs than control PMN after autologous stimulation. PMN from patients with severe vascular complications (pulmonary arterial hypertension, digital ulcers) produced more NETs than PMN from other SSc patients and their aberrant NET production appeared to be sustained over time. In patients with pulmonary interstitial disease or extensive cutaneous fibrosis, NET production was high at an early stage of the disease before progressively decreasing. Both serum factors and PMN activation status were involved in the enhanced production of NETs in SSc. Consequently, neutrophils and especially NETosis represent new physiopathological and therapeutic fields in SSc.
Published: 2020

24. Phenotype and outcome of pulmonary arterial hypertension patients carrying a TBX4 mutation

Author: Caroline Ovaert, Damien Bonnet, Gérald Simonneau, Céline Chabanne, Pierre Thoré, Olivier Sitbon, Marc Humbert, Marilyne Lévy, Claire Dauphin, Florent Soubrier, Laurent Savale, E. Boiffard, Xavier Jaïs, Martine Remy-Jardin, Amélie Servettaz, Barbara Girerd, Anne Guillaumot, Ari Chaouat, Frédéric Perros, Maria-Rosa Ghigna, David Montani, Vincent Cottin, Mélanie Eyries, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Pneumologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hypertension pulmonaire : physiopathologie et innovation thérapeutique (HPPIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Université Paris-Saclay, Centre Chirurgical Marie Lannelongue (CCML), Centre chirurgical Marie Lannelongue, Service d'Oncogénétique et Angiogénétique Moléculaire [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Service de génétique [CHU Pitié-Salpêtrière], Service de cardiologie pédiatrique [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), Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Clermont-Ferrand, CHU Pontchaillou [Rennes], Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Pulmonary and Respiratory Medicine, medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Hemodynamics, medicine.disease_cause, Gastroenterology, Vascular remodelling in the embryo, 03 medical and health sciences, 0302 clinical medicine, Diffusing capacity, Internal medicine, Parenchyma, medicine, Lung transplantation, Mutation, business.industry, Phenotype, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030228 respiratory system, Vascular resistance, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IntroductionTBX4 mutation causes small patella syndrome (SPS) and/or pulmonary arterial hypertension (PAH). The characteristics and outcomes of PAH associated with TBX4 mutations are largely unknown.MethodsWe report the clinical, functional, radiologic, histologic and haemodynamic characteristics and outcomes of heritable PAH patients carrying a TBX4 mutation from the French pulmonary hypertension (PH) network.Results20 patients were identified in 17 families. They were characterised by a median age at diagnosis of 29 years (0–76 years) and a female to male ratio of three. Most of the patients (70%) were in New York Heart Association (NYHA) functional class III or IV with a severe haemodynamic impairment (median pulmonary vascular resistance (PVR) of 13.6 (6.2–41.8) Wood units). Skeletal signs of SPS were present in 80% of cases. Half of the patients had mild restrictive or obstructive limitation and diffusing capacity of the lung for carbon monoxide (DLCO) was decreased in all patients. High-resolution computed tomography (HRCT) showed bronchial abnormalities, peri-bronchial cysts, mosaic distribution and mediastinal lymphadenopathies. PAH therapy was associated with significant clinical improvement. At follow-up (median 76 months), two patients had died and two had undergone lung transplantation. One-year, three-year and five-year event-free survival rates were 100%, 94% and 83%, respectively. Histologic examination of explanted lungs revealed alveolar growth abnormalities, major pulmonary vascular remodelling similar to that observed in idiopathic pulmonary arterial hypertension (IPAH) and accumulation of cholesterol crystals within the lung parenchyma.ConclusionPAH due to TBX4 mutations may occur with or without skeletal abnormalities across a broad age range from birth to late adulthood. PAH is usually severe and associated with bronchial and parenchymal abnormalities.
Published: 2020

25. Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy

Author: Mignard, Claire, Maho-Vaillant, Maud, Golinski, Marie-Laure, Balayé, Pierre, Prost-Squarcioni, Catherine, Houivet, Estelle, Calbo, Sé Bastien, Labeille, Bruno, Picard-Dahan, Catherine, Konstantinou, Maria Polina, Chaby, Guillaume, Richard, Marie-Aleth, Bouaziz, Jean-David, Duvert-Lehembre, Sophie, Delaporte, Emmanuel, Bernard, Philippe, Caux, Frédéric, Alexandre, Marina, Ingen-Housz-Oro, Saskia, Vabres, Pierre, Quéreux, Gaelle, Dupuy, Alain, Debarbieux, Sebastien, Avenel-Audran, Martine, d'Incan, Michel, Bedane, Christophe, Beneton, Nathalie, Jullien, Denis, Dupin, Nicolas, Misery, Laurent, Machet, Laurent, Beylot-Barry, Marie, Dereure, Olivier, Sassolas, Bruno, Bénichou, Jacques, Joly, Pascal, Hebert, Vivien, Calbo, Sébastien, Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-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), Unité de biostatistiques [CHU Rouen], University Hospital of St-Etienne, Department of Dermatology, Service de Dermatologie, Hôpital Bichat, AP-HP, Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Département de dermatologie, CHU Marseille, CHU Marseille, Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Hôpital Claude Huriez [Lille], CHU Lille, Immunodermatologie, Cytokines, Cancer - EA 7319 (ICA), Université de Reims Champagne-Ardenne (URCA), Service de dermatologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Henri Mondor, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Service de Dermatologie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Service de Dermatologie [CHU Limoges], CHU Limoges, Centre Hospitalier Le Mans (CH Le Mans), Club Rhumatismes et Inflammation, EA1833, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de dermatologie, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Bordeaux [Bordeaux], Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Charles Nicolle [Rouen], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de Dermatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), CHU Henri Mondor [Créteil], Université d'Angers (UA)-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)-Université d'Angers (UA)-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), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
Subjects: integumentary system, immune system diseases, [SDV]Life Sciences [q-bio], education, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances
Abstract: International audience; Importance: Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus.Objective: To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab.Design, setting, and participants: This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019.Exposure: Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen.Main outcomes and measures: Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti-desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated.Results: Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24]; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab.Conclusions and relevance: The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy.Trial registration: NCT00784589.
Published: 2020

26. Feasibility and healthcare costs of superpotent topical corticosteroid therapy in bullous pemphigoid: a prospective, observational study in an academic centre in France

Author: C. Muller, C. Vanhaecke, M.-A. Viguier, A. Clapé, Philippe Bernard, J. Plée, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: medicine.medical_specialty, Topical Corticosteroid Therapy, [SDV]Life Sciences [q-bio], Dermatology, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Adrenal Cortex Hormones, Health care, Pemphigoid, Bullous, medicine, Humans, 030212 general & internal medicine, Prospective Studies, ComputingMilieux_MISCELLANEOUS, business.industry, Health Care Costs, medicine.disease, 3. Good health, Feasibility Studies, Observational study, Bullous pemphigoid, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2020

27. Factors Associated With Short-term Relapse in Patients With Pemphigus Who Receive Rituximab as First-line Therapy

Author: Mignard, Claire, Maho-Vaillant, Maud, Golinski, Marie-Laure, Balayé, Pierre, Prost-Squarcioni, Catherine, Houivet, Estelle, Calbo, Sé´bastien, Labeille, Bruno, Picard-Dahan, Catherine, Konstantinou, Maria, Chaby, Guillaume, Richard, Marie-Aleth, Bouaziz, Jean-David, Duvert-Lehembre, Sophie, Delaporte, Emmanuel, Bernard, Philippe, Caux, Frédéric, Alexandre, Marina, Ingen-Housz-Oro, Saskia, Vabres, Pierre, Quereux, Gaëlle, Dupuy, Alain, Debarbieux, Sébastien, Avenel-Audran, Martine, D’Incan, Michel, Bédane, Christophe, Bénéton, Nathalie, Jullien, Denis, Dupin, Nicolas, Misery, Laurent, Machet, Laurent, Beylot-Barry, Marie, Dereure, Olivier, Sassolas, Bruno, Benichou, Jacques, Joly, Pascal, Hébert, Vivien, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; ; for the French Study Group on Autoimmune Bullous Skin Diseases IMPORTANCE Rituximab and short-term corticosteroid therapy are the criterion standard treatments for patients with newly diagnosed moderate to severe pemphigus. OBJECTIVE To examine factors associated with short-term relapse in patients with pemphigus treated with rituximab. DESIGN, SETTING, AND PARTICIPANTS This post hoc analysis of a randomized clinical trial (Comparison Between Rituximab Treatment and Oral Corticosteroid Treatment in Patients With Pemphigus [RITUX 3]) conducted from January 1, 2010, to December 31, 2015, included patients from 20 dermatology departments of tertiary care centers in France from the RITUX 3 trial and 3 newly diagnosed patients treated according to the trial protocol. Data analysis was performed from February 1 to June 30, 2019. EXPOSURE Patients randomly assigned to the rituximab group in the RITUX 3 trial and the 3 additional patients were treated with 1000 mg of intravenous rituximab on days 0 and 14 and 500 mg at months 12 and 18 combined with a short-term prednisone regimen. MAIN OUTCOMES AND MEASURES Baseline (pretreatment) clinical and biological characteristics (Pemphigus Disease Area Index [PDAI] score, ranging from 0-250 points, with higher values indicating more severe disease) and changes in anti-desmoglein (DSG) 1 and anti-DSG3 values as measured by enzyme-linked immunosorbent assay during the 3 months after rituximab treatment were compared between patients with disease relapse and those who maintained clinical remission during the first 12 months after treatment. The positive and negative predictive values of these factors were calculated. RESULTS Among 47 patients (mean [SD] age, 54.3 [17.0] years; 17 [36%] male and 30 [64%] female) included in the study, the mean (SD) baseline PDAI score for patients with relapsing disease was higher than that of the patients with nonrelapsing disease (54 [33] vs 28 [24]; P = .03). At month 3, 7 of 11 patients with relapsing disease (64%) vs 7 of 36 patients with nonrelapsing disease (19%) had persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher (P = .01). A PDAI score of 45 or higher defining severe pemphigus and/or persistent anti-DSG1 antibody values of 20 IU/mL or higher and/or anti-DSG3 antibody values of 130 IU/mL or higher at month 3 provided a positive predictive value of 50% (95% CI, 27%-73%) and a negative predictive value of 94% (95% CI, 73%-100%) for the occurrence of relapse after rituximab. CONCLUSIONS AND RELEVANCE The findings suggest that initial PDAI score and changes in anti-DSG antibody values after the initial cycle of rituximab might help differentiate a subgroup of patients with high risk of relapse who might benefit from maintenance rituximab infusion at month 6 from a subgroup of patients with low risk of relapse who do not need early maintenance therapy. TRIAL REGISTRATION NCT00784589
Published: 2020

28. Diagnosis and Management of Pemphigus: recommendations by an International Panel of Experts

Author: Katarzyna Wozniak, Catherine Prost-Squarcioni, Savaş Yayli, Branka Marinović, Donna A. Culton, Michael Hertl, Guiseppe Cianchini, Snejina Vassileva, Dedee F. Murrell, Aikaterini Patsatsi, Marwah A. Saleh, Sergei A. Grando, Pilar Iranzo, Dimitrios Ioannides, Annette Czernik, Aimee S. Payne, Claudio Feliciani, Johann W. Bauer, Francis Palisson, Luca Borradori, Jun Yamagami, Valeria Aoki, Karen E. Harman, Soner Uzun, Hideyuki Ujiie, Philippe Bernard, M. Peter Marinkovich, Daniel Mimouni, Richard Groves, Enno Schmidt, Cezary Kowalewski, Russell P. Hall, Pascal Joly, Hana Jedličková, John J. Zone, Neil J. Korman, Kossara Drenovska, Soo Chan Kim, Julia S. Lehman, Sharon Baum, Masayuki Amagai, Frédéric Caux, Adela R. Cardones, José M. Mascaró, Takashi Hashimoto, Victoria P. Werth, Emanual Michael Maverakis, Animesh A. Sinha, David P. Fivenson, Marcel F. Jonkman, Hiroshi Shimizu, Rüdiger Eming, Sandra Pena, Ron J. Feldman, Detlef Zillikens, Luis A. Diaz, Ayşe Akman-Karakaş, Maryam Daneshpazhooh, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), INSERM U1234, OSA (XLIM-OSA), XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS)-Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Hospital of the University of Pennsylvania (HUP), Perelman School of Medicine, University of Pennsylvania [Philadelphia]-University of Pennsylvania [Philadelphia], Universität Bern [Bern], Immunodermatologie, Cytokines, Cancer - EA 7319 (ICA), Service de dermatologie [Avicenne], Hôpital Avicenne-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13), Service de dermatologie [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Akdeniz University, St. John's Institute of Dermatology, London School of Medicine, Stanford University [Stanford], Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Stanford University
Subjects: Standardization, Delphi Technique, [SDV]Life Sciences [q-bio], Delphi method, Severity of Illness Index, 030207 dermatology & venereal diseases, 0302 clinical medicine, Medicine, CD20 inhibitor, guidelines, skin and connective tissue diseases, health care economics and organizations, computer.programming_language, Majority opinion, integumentary system, treatment, Academies and Institutes, Treatment options, Plasmapheresis, Combined Modality Therapy, 3. Good health, consensus, pemphigus foliaceus, pemphigus vulgaris, Europe, 030220 oncology & carcinogenesis, Combination, Practice Guidelines as Topic, Administration, Intravenous, Rituximab, Venereology, Consensus, Clinical Sciences, education, 610 Medicine & health, Dermatology, Article, 03 medical and health sciences, Drug Therapy, Humans, Immunologic Factors, Generalizability theory, CD20, Antigens, Glucocorticoids, Medical education, business.industry, Dermatology & Venereal Diseases, business, computer, Delphi, Pemphigus, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Background-Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. Objective-We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. Methods-A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. Results-The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. Limitations-Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. Conclusions-We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus. Keywords CD20 inhibitor; consensus; guidelines; pemphigus foliaceus; pemphigus vulgaris; treatment Pemphigus encompasses a spectrum of rare mucocutaneous bullous diseases that are autoimmune in origin. Because of the rarity of these diseases, it can take patients months before their pemphigus is diagnosed, during which time many are treated for other blistering diseases. 1,2 Even once the diagnosis has been made, treatment regimens can vary greatly, as
Published: 2020

29. B-cell depletion induces a shift in self antigen specific B-cell repertoire and cytokine pattern in patients with bullous pemphigoid

Author: Michael Hertl, Anne Dompmartin, Natacha Colliou, Nicolas Berkani, Philippe Bernard, Anis Larbi, Pascal Joly, Annick Lim, Guillaume Chaby, Marie-Laure Golinski, Gaëtan Riou, Frédérique Caillot, Sébastien Calbo, Philippe Musette, Emmanuel Delaporte, Christophe Bedane, UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Dermatologie [Rouen], Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: 0301 basic medicine, medicine.drug_class, medicine.medical_treatment, lcsh:Medicine, Monoclonal antibody, Article, 03 medical and health sciences, 0302 clinical medicine, medicine, Receptor, lcsh:Science, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, biology, business.industry, lcsh:R, medicine.disease, 3. Good health, 030104 developmental biology, Cytokine, Polyclonal antibodies, Immunology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Tumor necrosis factor alpha, Rituximab, lcsh:Q, Bullous pemphigoid, Antibody, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.drug
Abstract: Bullous Pemphigoid is the most common auto-immune bullous skin disease. It is characterized by the production of auto-antibodies directed against 2 proteins of the hemi-desmosome (BP180 and BP230). We assessed the efficacy and mechanisms of action of rituximab, an anti-CD20 monoclonal antibody, in 17 patients with severe and relapsing type of bullous pemphigoid. The phenotype, cytokine gene expression, and rearrangement of BP180-specific B-cell receptor genes were performed over 2 years following treatment. At the end of the study, 5 patients had died, 3 had withdrawn from the study, and 9 patients were in complete remission. The one- and two-year relapse rates were 44.1% (95% Confidence Interval (CI): 21.0–76.0%) and 66.5%, (95% CI: 38.4–91.4%), respectively. Phenotypic analyses confirmed dramatic B-cell depletion, which lasted for 9 to 12 months. The ELISA values of serum anti-BP180 antibodies and the frequency of BP180-specific circulating B cells decreased dramatically following treatment, which paralleled the improvement of skin lesions. During B-cell reconstitution, a polyclonal IgM repertoire appeared and a shift in the rearrangement of the B-cell receptor genes of BP180-specific circulating B cells was observed. Concurrently, we observed a decrease of IL-15, IL-6 and TNFα expressing BP180-specific B cells, and the emergence of IL-10 and IL-1RA-expressing BP180-specific IgM+ B cells in patients in complete remission off therapy, suggesting the functional plasticity of BP180-specific auto-immune B cells after rituximab treatment.
Published: 2019

30. Rituximab is an effective treatment in patients with pemphigus vulgaris and demonstrates a steroid‐sparing effect

Author: Bruno Sassolas, Frédéric Caux, Olivier Dereure, Saskia Ingen-Housz-Oro, E. Csinady, Estelle Houivet, D.M. Chen, Jean-David Bouaziz, C. Prost‐Squarcioni, S. Duvert-Lehembre, Sébastien Calbo, P. Bernard, Pierre Vabres, Nicolas Dupin, L. Gearhart, Pascal Joly, Laurent Machet, Jacques Benichou, A. Odueyungbo, Carle Paul, Philippe Musette, Gaëlle Quéreux, Sébastien Debarbieux, Alain Dupuy, Catherine Picard-Dahan, Nathalie Beneton, Emmanuel Delaporte, Maud Maho-Vaillant, Michel D'Incan, Marie-Laure Golinski, Denis Jullien, Frédérique Caillot, P.B. Lehane, Marie Aleth Richard, Bruno Labeille, Laurent Misery, Christophe Bedane, M. Alexandre, Vivien Hébert, Martine Avenel-Audran, M. Cheu, Marie Beylot-Barry, Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Physiopathologie, Autoimmunité, maladies Neuromusculaires et THErapies Régénératrices (PANTHER), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de biostatistiques [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), University Hospital of St-Etienne, Department of Dermatology, Service de dermatologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'oncologie [Hôpital privé Toulon Hyères : Sainte Marguerite], Hôpital privé Toulon Hyères : Sainte Marguerite, Commissariat à l'Energie Atomique (CEA), Institut de Biologie et Technologies de Saclay, Hôpital Henri Mondor, Equipe GAD (LNC - U1231), Lipides - Nutrition - Cancer [Dijon - U1231] (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-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, Hôpital Claude Huriez [Lille], CHU Lille, Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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 Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Service de dermatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Institut Laue-Langevin (ILL), Calcul Thermodynamique, Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire Interuniversitaire de Biologie de la Motricité (LIBM ), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Université Paris Diderot - Paris 7 (UPD7)-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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, ILL, Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM), Hôpital Charles Nicolle [Rouen], Service de Dermatologie [CHU Saint-Etienne], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)-Université Jean Monnet - Saint-Étienne (UJM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])
Subjects: medicine.medical_specialty, Prednisolone, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Dermatology, Gastroenterology, law.invention, Antibodies, Monoclonal, Murine-Derived, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Prednisone, Internal medicine, Humans, Immunologic Factors, Medicine, In patient, Adverse effect, ComputingMilieux_MISCELLANEOUS, business.industry, Standard treatment, Pemphigus vulgaris, Original Articles, medicine.disease, Clinical Trial, 3. Good health, Treatment Outcome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Rituximab, business, Adjuvant, Immunosuppressive Agents, Pemphigus, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Summary Background Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid‐related adverse events (AEs) is unproven. Objectives To utilize data collected in a French investigator‐initiated, phase III, open‐label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. Methods This was an independently conducted post hoc analysis of the moderate‐to‐severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg−1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg−1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24‐month efficacy and safety results were also reported. Results At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab‐plus‐prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS‐related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. Conclusions In patients with moderate‐to‐severe PV, rituximab plus short‐term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life‐threatening CS‐related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus.Corticosteroids, a standard first‐line treatment for PV, have significant side‐effects.Although their effects are unproven, adjuvant corticosteroid‐sparing agents are routinely used to minimize steroid exposure and corticosteroid‐related side‐effects.There is evidence that the anti‐CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator‐initiated trial.Rituximab plus prednisone had a steroid‐sparing effect and more patients achieved complete remission off prednisone.Fewer patients experienced grade 3 or grade 4 steroid‐related adverse events than those on prednisone alone.This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate‐to‐severe PV., Linked Comment: Scorer et al. Br J Dermatol 2020; 182:1078–1079.
Published: 2019

31. Actualités dans la physiopathologie de la sclérodermie systémique : vers de nouvelles opportunités thérapeutiques

Author: Frank Antonicelli, Amélie Servettaz, B.N. Pham, A. Robbins, K. Didier, D. Giusti, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: 030203 arthritis & rheumatology, 0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, [SDV]Life Sciences [q-bio], Gastroenterology, Internal Medicine, 3. Good health
Abstract: Resume La sclerodermie systemique est une connectivite rare, caracterisee par une fibrose de la peau et de differents organes internes, une vasculopathie systemique et des anomalies de l’immunite innee et adaptative. Des dysfonctions des fibroblastes, des cellules endotheliales et des lymphocytes, mais egalement d’autres cellules de l’immunite sont de mieux en mieux decrites, meme si l’origine exacte et la chronologie de ces anomalies restent inconnues. Le stress oxydatif semble jouer un role cle dans la maladie. Il semble en effet implique tres precocement dans le developpement de la fibrose, de la vasculopathie et dans les anomalies de la tolerance immunitaire observees chez tous les patients, bien que l’expression de la maladie soit tres heterogene. Ce stress semble influence par des facteurs genetiques et environnementaux. Sur le plan therapeutique, il n’existe actuellement aucun traitement curatif. Des immunosuppresseurs et des molecules actives sur l’atteinte vasculaire sont proposes dans certains cas avec une efficacite variable d’un patient a l’autre et globalement moderee. Seule l’autogreffe de cellules souches hematopoietiques, reservee aux formes severes ou rapidement progressives, a montre une regression de la fibrose prolongee ainsi qu’une reduction de la morbi-mortalite, mais expose a une potentielle toxicite. Au cours de la derniere decennie, de nouveaux mecanismes impliques dans la physiopathologie de la sclerodermie systemique ont ete decouverts, offrant de nouvelles perspectives therapeutiques. Dans cette revue, nous nous proposons de faire le point sur les recentes avancees dans la connaissance de la physiopathologie de la sclerodermie systemique et leurs implications dans la prise en charge therapeutique, actuelle et future.
Published: 2019

32. Severe Attack of Henoch-Schönlein Purpura With Neurological Involvement During Adalimumab Treatment for Crohn’s Disease

Author: Guillaume Cadiot, Emmanuelle Diaz, Jean-Hugues Salmon, Morgane Condamina, Céline Jamart, Manuelle Viguier, Anne Durlach, Jeffrey Loget, PSA Peugeot - Citroën (PSA), PSA Peugeot Citroën (PSA), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Hôpital universitaire Robert Debré [Reims], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Maison Blanche, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Henoch-Schonlein purpura, [SDV]Life Sciences [q-bio], Anti-Inflammatory Agents, Disease, Gastroenterology, Severity of Illness Index, Endoscopy, Gastrointestinal, 0302 clinical medicine, Crohn Disease, adalimumab, ComputingMilieux_MISCELLANEOUS, Skin, Crohn's disease, Peripheral Nervous System Diseases, General Medicine, 3. Good health, Henoch-Schönlein purpura, Purpura, Treatment Outcome, 030211 gastroenterology & hepatology, Tumor necrosis factor alpha, Administration, Intravenous, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], medicine.symptom, Vasculitis, Gastrointestinal Hemorrhage, medicine.drug, medicine.medical_specialty, IgA Vasculitis, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Adalimumab, Humans, endoscopy, Adverse effect, Glucocorticoids, 030203 arthritis & rheumatology, Dose-Response Relationship, Drug, business.industry, Electromyography, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, Tumor Necrosis Factor Inhibitors, pathology, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: Tumour necrosis factor-α [TNF-α] inhibitors have revolutionised the management of chronic inflammatory conditions. A number of cutaneous adverse events have been reported with TNF inhibition, including vasculitis. Most reactions are mild and rarely warrant treatment withdrawal. Here we describe a patient with Crohn’s disease treated with adalimumab in whom severe multivisceral Henoch-Schönlein purpura developed, including neurological involvement, requiring definitive TNF blocker withdrawal.
Published: 2019

33. Low cardiovascular risk and poor quality of life associated with tobacco use and skin infections in adult atopic dermatitis: result of a French multicenter study

Author: Marie Chuffart‐Delplanque, Martine Bagot, Jean-David Bouaziz, Angèle Soria, Anne-Sophie Darrigade, Delphine Staumont-Sallé, C. Fite, Audrey Nosbaum, Marie Jachiet, Sylvie Chevret, Adèle de Masson, Manuelle Viguier, Julien Seneschal, Anne‐Clémence Carriou, Annick Barbaud, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: Adult, Male, medicine.medical_specialty, Tobacco use, Dermatology, Skin infection, Severity of Illness Index, Poor quality, Dermatitis, Atopic, 030207 dermatology & venereal diseases, 03 medical and health sciences, Tobacco Use, Young Adult, 0302 clinical medicine, Risk Factors, Medicine, Humans, Skin Diseases, Infectious, Adult atopic dermatitis, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, business.industry, Atopic dermatitis, medicine.disease, 3. Good health, Infectious Diseases, Neuropsychiatric disorder, Multicenter study, Cardiovascular Diseases, Quality of Life, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2019

34. NET Formation in Bullous Pemphigoid Patients With Relapse Is Modulated by IL-17 and IL-23 Interplay

Author: Delphine, Giusti, Estela, Bini, Christine, Terryn, Kevin, Didier, Sébastien, Le Jan, Grégory, Gatouillat, Anne, Durlach, Stéphane, Nesmond, Celine, Muller, Philippe, Bernard, Frank, Antonicelli, Bach Nga, Pham, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Plateforme en Imagerie Cellulaire et Tissulaire (PICT), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), and Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)
Subjects: Male, bullous pemphigoid, Neutrophils, Immunology, Anti-Inflammatory Agents, neutrophil extracellular traps, Tyramine, Acetates, Extracellular Traps, Methylprednisolone, Translational Research, Biomedical, Recurrence, Pemphigoid, Bullous, cytokine, Humans, Prospective Studies, Aged, Original Research, eosinophil extracellular traps, Aged, 80 and over, Interleukin-17, autoimmunity, Middle Aged, Eosinophils, inflammation, Interleukin-23 Subunit p19, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female
Abstract: International audience; Background: DNA extracellular traps (ETs), released by neutrophils (NETs), or eosinophils (EETs), play a pathogenic role in several autoimmune disorders. However, to date, NETs have never been investigated in bullous pemphigoid (BP) with respect to clinical and immunological activities, both at baseline and at time of relapse which have been characterized with specific IL-17 and IL-23 patterns. Objective: We sought to assess whether ETs were associated with BP as well as the relative contribution of IL-17 axis cytokines to NET induction. Methods: Skin biopsy specimens were obtained from 11 patients with BP. Immuno-detection of neutrophils and eosinophils combined to DNA staining allowed us to investigate the in-situ presence of NETs and EETs using confocal scanning microscopy. NETs release was evaluated ex vivo by stimulating polymorphonuclear cells from BP patients with BP biological fluids in presence of IL-17A and IL-23 or of glucocorticoids. Results: At baseline, ETs were observed in BP lesions at the site of dermal-epidermal cleavage. Despite an important infiltrate of eosinophils, ETs were essentially associated with neutrophils in situ and were not related to BP clinical activity at diagnosis. In situ observation of NETs was associated in 6 among 8 patients with serum capacity of NET induction. Notably both blister fluid and sera from BP patients at diagnosis and at time of relapse could induce NET formation ex vivo. In contrast, a longitudinal investigation showed a decrease of NET formation with time of treatment in patients undergoing remission. Mimicking relapse, complementation of sera from BP patients with ongoing remission with either IL-17A or IL-23 increased NET formation. Conversely, IL-17A inhibited NET formation induced by serum from BP patients with relapse supplemented or not with IL-23. Finally, glucocorticoids also inhibited NET formation ex vivo in BP. Conclusion: NET formation is an associated phenomenon with BP. Furthermore, we showed that IL-23 favored NET formation, whereas the effects of IL-17A are environment dependent. Indeed, IL-17A displayed a protective effect on NET formation when associated with IL-23, showing for the first-time differential effects of these two cytokines in BP.
Published: 2019

35. Diagnostic Utility of Separate Anti-Ro60 and Anti-Ro52/TRIM21 Antibody Detection in Autoimmune Diseases

Author: Ailsa Robbins, Maxime Hentzien, Segolene Toquet, Kevin Didier, Amelie Servettaz, Bach-Nga Pham, Delphine Giusti, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Vieillissement, Fragilité (VIEFRA - EA 3797), and Hôpital universitaire Robert Debré [Reims]
Subjects: Male, 0301 basic medicine, systemic lupus, Anti-nuclear antibody, Autoantigens, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, RNA, Small Cytoplasmic, Lupus Erythematosus, Systemic, Immunology and Allergy, ComputingMilieux_MISCELLANEOUS, Myositis, Original Research, Aged, 80 and over, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Lupus anticoagulant, biology, Systemic lupus, Middle Aged, anti-Ro60 antibodies, Connective tissue disease, 3. Good health, Sjogren's Syndrome, Ribonucleoproteins, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Antibodies, Antinuclear, Antibodies, Antiphospholipid, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, Antibody, Antibody detection, lcsh:Immunologic diseases. Allergy, Adult, Adolescent, anti-Ro52 antibodies, Immunology, Young Adult, 03 medical and health sciences, medicine, Humans, autoimmune diseases, In patient, Aged, Retrospective Studies, Scleroderma, Systemic, business.industry, anti-SSA antibodies, medicine.disease, primary Sjögren's syndrome, 030104 developmental biology, connective tissue disease, biology.protein, lcsh:RC581-607, business, TRIM21, 030215 immunology
Abstract: International audience; Anti-SS-A antibodies are often sought for in autoimmune diseases diagnosis. Two different target proteins have actually been identified: Ro52 and Ro60. Clinical and immunological associations seem different depending on anti-Ro52 or anti-Ro60 antibodies presence. However, due to a heterogeneous presentation in the literature, some immunology laboratories in France have stopped providing anti-Ro52 antibody findings. We report here a new hospital study designed to determine the diagnostic utility of the separate detection of anti-Ro52 and anti-Ro60 antibodies. We conducted a retrospective, observational study, including every adult patient with positive antinuclear antibodies (ANA) tested in our immunology laboratory, and associated with anti-Ro52 and/or anti-Ro60 antibodies, between 2011 and 2014. Out of 13032 sera tested for ANA, 399 adults had antibodies to Ro52 and/or Ro60; 81.7% were female, with a mean age of 54.5 ± 17.0 years. Anti-Ro52 antibodies were found in 75.7% of the patients and anti-Ro60 antibodies in 56.9%. Among them, 43.1% were classified in the Ro52 + Ro60- group, 32.6% in the Ro52 + Ro60 + group and 24.3% in the Ro52-Ro60+ group. In the Ro52-Ro60+ group, systemic lupus was the most frequent diagnosis (48.5%), with a possible association with antiphospholipid antibodies (anti-cardiolipin antibodies: OR 2.5 (CI95 [1.0–5.0], p = 0.05) and lupus anticoagulant {OR 3.6 (CI95 [1.10–10.0] p = 0.02)}. In the Ro52+Ro60+, primary Sjögren Syndrome was the most likely (OR 4.2 95% CI [2.1–8.3] p < 10−4), especially in patients Ro52+Ro60+La+. Patients with isolated anti-Ro52 had a wider variety of diseases associated, but among auto-immune diseases they were more prone to inflammatory myositis (OR 10.5 [1.4–81.7], p = 0.02) and inflammatory rheumatism (OR 4.6 [1.6–13.8], p = 0.006) in contrast to systemic lupus (OR 0.2 [0.1–0.3], p < 10−4) or primary Sjögren's syndrome (OR 0.1 [0.06–0.2], p < 10−4). We therefore suggest that, when anti-ENA antibodies are prescribed, it should include separate anti-Ro52 and anti-Ro60 antibodies determination. To go even further, we would like to suggest a change in ENA nomenclature to avoid confusion, abandoning the anti-SS-A label in favor of the anti-Ro52/TRIM21 or anti-Ro60 antibody for a clearer designation.
Published: 2019

36. French guidelines on the use of systemic treatments for moderate‐to‐severe psoriasis in adults

Author: A.P. Villani, Bernard Guillot, Marie Tauber, M. Viguier, Florent Amatore, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre de Recherche sur la Peau [Toulouse], Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Preuves en Dermatologie, and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Adult, medicine.medical_specialty, medicine.medical_treatment, MEDLINE, Guidelines and Position Statements, MESH: Algorithms, Dermatologic Agents/therapeutic use, Psoriasis/drug therapy, Severity of Ilness Index, Dermatology, Guidelines, 030207 dermatology & venereal diseases, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Psoriasis, Severity of illness, medicine, Humans, [INFO]Computer Science [cs], Intensive care medicine, Therapeutic strategy, 030203 arthritis & rheumatology, business.industry, Moderate to severe psoriasis, Antibodies, Monoclonal, medicine.disease, Comorbidity, 3. Good health, Infectious Diseases, PUVA therapy, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; These guidelines were developed by the psoriasis research group of the French Society of Dermatology with the aim of providing updated decision-making algorithms for the systemic treatment of adult patients with moderate-to-severe psoriasis. Our algorithms were generated after rigorous evaluation of existing guidelines on the treatment of psoriasis and of publications concerning new systemic treatments, not yet incorporated into existing guidelines. A total of nine existing guidelines and 53 publications related to new systemic treatments were found to meet our criteria for use in the generation of the algorithms. We have proposed two new algorithms to assess therapeutic responses, both of which incorporate emerging criteria for evaluating treatment goals. Updated therapeutic strategy algorithms, incorporating both established and new systemic therapies, were also generated for the treatment of plaque psoriasis and psoriatic arthritis, together with recommendations for the treatment of particular forms of psoriasis and treatment of patients with comorbidities.
Published: 2019

37. Incidence and Mortality of Pemphigus in France

Author: Minocha, Rashi, Martin, Andrew, Chen, Andrew, Scolyer, Richard, Lyons, J, Mckenzie, Catriona, Madore, Jason, Halliday, Gary, Damian, Diona, Ns, Agar, Gm, Halliday, Rs, Barnetson, Hn, Ananthaswamy, Ac, Chen, Aj, Martin, Jelti, Lamia, Cordel, Nadège, Gillibert, André, Lacour, Jean-Philippe, Uthurriague, Claire, Doutre, Marie-Sylvie, Delaporte, Emmanuel, Duvert-Lehembre, Sophie, Quereux, Gaelle, Dupuy, Alain, Adamski, Henri, Bedane, Christophe, Misery, Laurent, Abasq Thomas, Claire, Fleuret, Camille, Bernard, Philippe, Chaby, Guillaume, D'Incan, Michel, Verneuil, Laurence, Litrowski, Noemie, Joly, Pascal, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: integumentary system, sense organs, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; AM. The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: a role for UVA in human skin carcinogenesis. Proc Natl Acad Sci USA 2004;101:4954e9. Bostom AG, Merhi B, Walker J, Robinson-Bostom L. More than skin deep? Potential nicotinamide treatment applications in chronic kidney transplant recipients. World J Transpl 2016;6:658e64.
Published: 2019

38. A new phototherapy regimen during winter as an add-on therapy, coupled with oral vitamin D supplementation, for the long-term control of atopic dermatitis study protocol for a multicentre, randomized, crossover, pragmatic trial - the PRADA trial

Author: Droitcourt, Catherine, Barbarot, Sébastien, Maruani, Annabel, Darrieux, Laure, Misery, Laurent, Brenaut, Emilie, Adamski, Henri, Chabbert, Cécile, Vermersch, Annie, Weiborn, Marie, Seneschal, Julien, Taïeb, Alain, Plantin, Patrice, Maillard, Hervé, Phan, Alice, Skowron, François, Viguier, Manuelle, Staumont-Salle, Delphine, Nosbaum, Audrey, Soria, Angèle, Barbaud, Annick, Oger, Emmanuel, Dupuy, Alain, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche en Pharmaco-épidémiologie et Recours aux Soins (REPERES), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), French Ministry of Social Affairs and Health, France, Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP), Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), and Jonchère, Laurent
Subjects: pragmatic trial, Time Factors, Anti-Inflammatory Agents, Administration, Oral, vitamin D, add-on therapy, Administration, Cutaneous, Dermatitis, Atopic, Study Protocol, Double-Blind Method, Pragmatic Clinical Trials as Topic, Humans, Multicenter Studies as Topic, Cholecalciferol, Atopic dermatitis, Cross-Over Studies, long-term control, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Combined Modality Therapy, Treatment Outcome, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Dietary Supplements, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Ultraviolet Therapy, France, Seasons, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, phototherapy
Abstract: Background Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates. Methods This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter. Discussion This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health. Trial registration ClinicalTrials.gov Identifier: NCT02537509, first received: 1 September 2015. Electronic supplementary material The online version of this article (10.1186/s13063-019-3276-9) contains supplementary material, which is available to authorized users.
Published: 2019

39. IL-23/IL-17 Axis Activates IL-1β-Associated Inflammasome in Macrophages and Generates an Auto-Inflammatory Response in a Subgroup of Patients With Bullous Pemphigoid

Author: Sébastien Le Jan, Céline Muller, Julie Plee, Anne Durlach, Philippe Bernard, Frank Antonicelli, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), and dormoy, valerian
Subjects: 0301 basic medicine, Male, bullous pemphigoid, Erythema, Inflammasomes, medicine.medical_treatment, Interleukin-1beta, Gene Expression, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Interleukin-23, 0302 clinical medicine, Pemphigoid, Bullous, Interleukin 23, Immunology and Allergy, Original Research, Aged, 80 and over, integumentary system, Interleukin-17, Inflammasome, Middle Aged, 3. Good health, macrophages, IL-17, Cytokine, Matrix Metalloproteinase 9, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, IL-1β, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Cytokines, Female, Bullous pemphigoid, Interleukin 17, Disease Susceptibility, medicine.symptom, medicine.drug, Signal Transduction, lcsh:Immunologic diseases. Allergy, Immunology, Context (language use), auto-inflammation, Proinflammatory cytokine, 03 medical and health sciences, inflammasome, medicine, Humans, Aged, Autoantibodies, business.industry, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, 030104 developmental biology, lcsh:RC581-607, business, Biomarkers, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, 030215 immunology
Abstract: International audience; Bullous Pemphigoid (BP) is a skin autoimmune blistering disease characterized by immune-mediated degradation of the dermo-epidermal junction and release of a large number of inflammatory cytokines. Interleukin-1β (IL-1β) is a pleiotropic pro-inflammatory cytokine associated with inflammasome activation and known to be pivotal in several auto-immune and auto-inflammatory diseases. We sought to clarify the presence of inflammasome-dependent IL-1β and to investigate its role in BP. Skin biopsy specimens (n = 13), serum (n = 60), blister fluid (n = 26), and primary inflammatory cells from patients with BP were used to investigate inflammasome activation and function. We here highlighted a differential occurrence of a functional in situ inflammasome in patients with BP, biologically distinguished by IL-1β and NLRP3 expression. Clinically, elevated IL-1β levels were associated with the presence of erythema and urticarial plaques reflecting the inflammatory phase preceding blister formation. We further identified IL-17 and IL-23 as important molecules favoring IL-1β expression in monocyte-derived macrophages from BP patients. Finally, we demonstrated the ability of IL-1β to stimulate the release of the matrix metalloproteinase-9 in those macrophages, reinforcing the role of IL-1β in the auto-amplification loop of the inflammatory response associated to BP. However, whether this inflammasome is an epiphenomenon associated with BP disease or constitutes an amplification inflammatory step in certain patients still need to be determined. In the context of a precision medicine approach, our findings allowed us to delineate a subgroup of patients with BP that showed similarities with auto-inflammatory diseases. Subsequently, this opens up alternative therapeutic strategies targeting IL-1β pathway in the aim to control the early, pre-blistering inflammatory phase. Ultimately, this could also help in reducing the detrimental effects associated with high doses of corticosteroids treatment.
Published: 2019

40. Assessment of TNF-α inhibitors in airway involvement of relapsing polychondritis

Author: Biya, Josette, Dury, Sandra, Perotin, Jeanne-Marie, Launois, Claire, Dewolf, Maxime, Deslée, Gaetan, Lebargy, François, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Immunité Adaptative et Fonctionnalité des Barrières Biologiques - EA 4683 (IMAB), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Pathologies Pulmonaires et Plasticité Cellulaire - UMR-S 1250 (P3CELL), Université de Reims Champagne-Ardenne (URCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), dormoy, valerian, Plasticité de l'épithélium respiratoire dans les conditions normales et pathologiques - UMR-S 903 (PERPMP), Université de Reims Champagne-Ardenne (URCA)-Centre Hospitalier Universitaire de Reims (CHU Reims)-Institut National de la Santé et de la Recherche Médicale (INSERM)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Service de Médecine Respiratoire [CHU Reims], Université de Picardie Jules Verne (UPJV), Hôpital Maison Blanche, Unité d'Aide Méthodologique, and Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims)
Subjects: [SDV]Life Sciences [q-bio], relapsing polychondritis, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, [SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy, TNF-a inhibitors, airways, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, TNF-α inhibitors
Abstract: International audience; Relapsing polychondritis (RP) is a rare immune-mediated disease affecting cartilaginous structures. Respiratory tract manifestations are frequent and constitute a major cause of morbidity and mortality. The present review of the literature was designed to assess the efficacy of tumor necrosis factor alpha (TNF-a) inhibitors in respiratory tract involvement of RP. A MEDLINE literature search was performed from January 2000 to December 2016 to identify all studies and case reports of anti-TNF-a therapy in RP. Articles published in English or French concerning patients with respiratory tract involvement were eligible. Two authors (JB, FL) independently reviewed and extracted data concerning each patient and 2 personal cases were added. Treatment efficacy was assessed according to systemic and/or respiratory criteria. A total of 28 patients (mean age: 41.6 years; 16 females/12 males) were included in the final analysis. Anti-TNF-a therapy was associated with improved health status and respiratory symptoms in 67.8% and 60.1% of cases, respectively. These results suggest that TNF-a inhibitors could be considered for the treatment of respiratory tract involvement of RP. Abbreviations: CT = computed tomography, FDG/PET = fluorodeoxyglucose positron emission tomography, RP = relapsing polychondritis, TNF-a = tumor necrosis factor alpha.
Published: 2019

41. Blister Fluid Induces MMP-9-Associated M2-Type Macrophages in Bullous Pemphigoid

Author: Riani, Meriem, Muller, Céline, Bour, Camille, Bernard, Philippe, Antonicelli, Frank, Le Jan, Sébastien, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), and Pommier, Arnaud
Subjects: bullous pemphigoid, [SDV.IMM] Life Sciences [q-bio]/Immunology, integumentary system, Macrophages, macrophage polarization, Immunology, autoimmunity, Exudates and Transudates, Macrophage Activation, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, Blister, Matrix Metalloproteinase 9, inflammation, Pemphigoid, Bullous, Humans, [SDV.IMM]Life Sciences [q-bio]/Immunology, MMP-9, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Original Research
Abstract: International audience; Bullous pemphigoid (BP) is a cutaneous autoimmune disease, characterized by an inflammatory cascade leading to blister formation. Although macrophages were shown to participate in BP pathophysiology, their role in the blister formation process still needs to be investigated. We here addressed the influence of serum and blister fluid (BF) from patients with BP on the polarization status of macrophages with regards to the metalloproteinase-9 (MMP-9) expression. We demonstrated that several markers related to the alternatively activated macrophage phenotype (M2) including IL-10, TARC, arginase, TNFα, and IL-1RA were meaningfully increased in BF of patients with BP. We further showed that BF, but not serum from patients with BP, significantly induced the expression of CD163, CD206, and IL-10 in BP monocyte-derived macrophages (MDMs). Notably IL-10 was the only cytokine to be correlated to the reference clinical score, BP disease activity index (BPDAI), especially to the inflammatory BPDAI subscore evaluating urticarial and erythematous skin lesions (r = 0.57, p = 0.0004). We also found elevated levels of MMP-9 to M2-type macrophages ex vivo and highlighted the presence of CD163+ MMP-9+ macrophages histologically, at skin lesional site. Finally, we showed that methylprednisolone reduced MMP-9 levels in MDMs without modifying the other M2 markers. All together these results strongly support the presence of M2-phenotype macrophages with pro-inflammatory properties susceptible to favor blister formation in BP.
Published: 2019

42. Characteristic Pattern of IL-17RA, IL-17RB, and IL-17RC in Monocytes/Macrophages and Mast Cells From Patients With Bullous Pemphigoid

Author: Stéphane Nesmond, Céline Muller, Richard Le Naour, Manuelle Viguier, Philippe Bernard, Frank Antonicelli, Sébastien Le Jan, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: Male, 0301 basic medicine, bullous pemphigoid, T-Lymphocytes, medicine.medical_treatment, medicine.disease_cause, Monocytes, Autoimmunity, Blister, 0302 clinical medicine, Pemphigoid, Bullous, Medicine, Immunology and Allergy, Mast Cells, Prospective Studies, Receptor, Original Research, Aged, 80 and over, Receptors, Interleukin-17, autoimmunity, Mast cell, 3. Good health, medicine.anatomical_structure, Cytokine, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Bullous pemphigoid, medicine.symptom, IL-17 receptors, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, Immunology, Inflammation, 03 medical and health sciences, Immune system, Internal medicine, Humans, RNA, Messenger, business.industry, Macrophages, Monocyte, medicine.disease, IL-17 isoforms, 030104 developmental biology, Endocrinology, inflammation, lcsh:RC581-607, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, 030215 immunology
Abstract: International audience; Inflammation is largely implicated in bullous pemphigoid (BP), the most frequent skin auto-immune blistering disease. IL-17, essentially IL-17A/F, has been involved in blister formation through regulation of protease production, and its specific serum profile within BP was related to disease outcome. However, relationships between IL-17 family ligands and receptors are quite complex with six different IL-17 isoforms, and five different receptors. We here aimed at clarifying the contribution of the IL-17 axis in BP by characterizing not only the expression of IL-17 receptor (IL-17R) members within immune cells isolated from BP patients (PMNs, n = 9; T-lymphocytes, n = 10; and monocytes, n = 10) but also the expression of IL-17 isoforms in sera (n = 83), and blister fluid (n = 31) of BP patients. We showed that at diagnosis, IL-17RA and IL-17RC expression were significantly increased in monocytes isolated from BP patients as compared to those from control subjects (p = 0.006 and p = 0.016, respectively). Notably, both IL-17RA and IL-17RC mRNA expression remained elevated in BP monocytes at time of relapse. We further demonstrated a significant increase of all IL-17 isoforms tested in BP blister fluid compared with BP serum (IL-17A, p < 0.0001; IL-17A/F, p < 0.0001; IL-17B, p = 0.0023; IL-17C, p = 0.0022; IL-17E, p < 0.0001). Among all, IL-17B was the only cytokine for which a significant decreased concentration within blister fluid was observed in BP patients with severe disease compared to patients with moderate disease (p = 0.012). We further evidenced a significant negative correlation between IL-17B levels and blister/erosion BPDAI subscore (r = −0.52, p = 0.003). We finally identified mast cells as a potential target of IL-17B in lesional skin of BP patients. In conclusion, we showed here that IL-17RA and IL-17RC expression in monocyte was associated with disease activity and evidenced in situ a negative correlation between BP disease activity and IL-17B, whose effects could be mediated by IL-17RB expressed by mast cell in BP lesional skin
Published: 2019

43. Facteurs pronostiques de la dermatomyosite à anticorps anti-MDA5 : sexe féminin et atteinte articulaire de bon pronostic

Author: Gaëlle Leroux, S. Toquet, S. Humbert, Christophe Deligny, Yurdagul Uzunhan, Bernard Bonnotte, Laure Gallay, Olivier Benveniste, Réseau français des myosites, Y. Allenbach, Romain Paule, Amélie Servettaz, Nicolas Limal, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), 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), Université Paris 13 (UP13), 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 [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), and IFP Energies nouvelles (IFPEN)
Subjects: [SDV]Life Sciences [q-bio], Gastroenterology, Internal Medicine
Abstract: Introduction Les dermatomyosites a anticorps anti-MDA5 (DM MDA5+) ont des atteintes extramusculaires au premier plan (lesions cutanees severes, arthralgies/arthrite, fievre) pouvant engager le pronostic vital (atteinte pulmonaire), alors que l’atteinte musculaire est peu marquee. Leur pronostic est sombre (25 % de mortalite) et il est important de definir des facteurs de risque de mortalite pour mieux definir la strategie therapeutique. L’objectif de cette etude est d’identifier des facteurs pronostiques chez les DM MDA5+. Materiels et methodes Nous avons realise une etude nationale multicentrique retrospective grâce au Reseau francais des myosites pour les DM MDA5+. Les criteres d’inclusion etaient : – un diagnostic de DM (definie selon les criteres de l’ENMC en 2004 : un debut progressif subaigu, une faiblesse musculaire plutot proximale, une atteinte cutanee typique comme un erytheme lilace des paupieres, des papules de Gottron ou un erytheme du decollete et une atrophie perifasciculaire a la biopsie musculaire) ; – la positivite des anticorps anti-MDA5. Les recueils des donnees cliniques, paracliniques et evolutives ont ete realises a partir des dossiers des patients. Resultats Quarante et un patients ont ete identifies. L’âge moyen etait de 44 ans (± 16,5) avec un sex-ratio femme/homme de 1,4. Au diagnostic 92 % patients presentaient une atteinte pulmonaire et 87 % une atteinte cutanee. Un tiers (31 %) des patients ont presente une atteinte pulmonaire rapidement progressive (RPILD definie par une aggravation des lesions au scanner thoracique ou une aggravation des EFR pendant une duree inferieure ou egale a 3 mois). Les atteintes articulaires et musculaires (deficit moteur ou elevation des CK) etaient observees respectivement dans 75 % et 51 % des cas. La duree moyenne de suivi etait de 41,2 mois (± 61,3). La plupart des patients ont beneficie de corticosteroides (98 %) et d’immunosuppresseurs (83 %, dont 24 % du cyclophosphamide et 15 % des inhibiteurs des calcineurines) ou de rituximab (7 %), plus ou moins associes a des echanges plasmatiques (20 %) et/ou des immunoglobulines intraveineuses (15 %) selon leur severite. Le taux de mortalite etait de 22 %, avec des 44 % des deces survenus dans les 3 mois suivants le diagnostic. Les deces etaient dus a l’atteinte respiratoire dans 67 % des cas. Parmi les patients vivants, 52 % ont presente au moins une rechute, avec le plus frequemment une rechute pulmonaire (45 % des patients rechuteurs). L’analyse univariee identifie 3 variables liees au deces. Comme attendu les signes de gravite immediate respiratoire ont ete identifies avec une hypoxie severe (paO2 Conclusion Comme attendu, la severite initiale de l’atteinte pulmonaire (RPILD et hypoxie profonde) est un facteur pronostique pejoratif. Cette etude suggere pour la premiere fois que le sexe feminin et l’existence d’une atteinte articulaire seraient des elements de bon pronostic a prendre en compte dans la strategie therapeutique chez les patients sans signe de gravite pulmonaire immediate.
Published: 2018

44. The Interleukin-17 Family of Cytokines in Breast Cancer

Author: Christian Garbar, Yacine Merrouche, Jérôme Giustinniani, Frank Antonicelli, Joseph Fabre, Armand Bensussan, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Institut Jean Godinot [Reims], UNICANCER, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Inserm UMR-S 976, Institut National de la Santé et de la Recherche Médicale (INSERM), Pommier, Arnaud, and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: 0301 basic medicine, medicine.medical_treatment, Review, interleukin-17, lcsh:Chemistry, 0302 clinical medicine, lcsh:QH301-705.5, Spectroscopy, new target, biology, General Medicine, 3. Good health, Computer Science Applications, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Interleukin 17, immunotherapy, medicine.symptom, Signal Transduction, [SDV.IMM] Life Sciences [q-bio]/Immunology, Inflammation, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Models, Biological, Catalysis, Proinflammatory cytokine, Inorganic Chemistry, 03 medical and health sciences, Breast cancer, breast cancer, [SDV.CAN] Life Sciences [q-bio]/Cancer, protumor effects, Cyclin-dependent kinase, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, PI3K/AKT/mTOR pathway, business.industry, Organic Chemistry, Cancer, Immunotherapy, medicine.disease, 030104 developmental biology, antitumor effects, lcsh:Biology (General), lcsh:QD1-999, Cancer research, biology.protein, business
Abstract: International audience; Breast cancer (BC) is the most common cancer in women worldwide and remains a major cause of mortality with an expected 137,000 death this year in Europe. Standard management of metastatic BC comprises hormonotherapy, chemotherapy, and targeted therapies. Cyclin dependent kinase (CDK) and mammalian target of rapamycin (mTOR) inhibitors have recently proved their efficiency in hormonal receptor expressing BC. Checkpoint proteins inhibition is being evaluated in phase 3 studies. Since inflammation is constantly present in cancers, research teams have focused their attention on the interleukin-17 (IL-17) family of proinflammatory cytokines. Preclinical experiments have reported both pro and antitumor effects depending on the conditions. In the present article, we review the accumulating evidences about the roles of IL-17 in BC and discuss whether this family of cytokines could be a new target in anticancer treatments.
Published: 2018

45. Recommandations du GEFPICS pour la prise en charge des prélèvements dans le cadre du traitement néoadjuvant du cancer du sein

Author: Maran-Gonzalez, Aurélie, Franchet, Camille, Duprez-Paumier, Raphaelle, Antoine, Martine, Barlier, Catherine, Bécette, Véronique, Berghian, Anca, Blanc-Fournier, Cécile, Brabencova, Eva, Charafe-Jauffret, Emmanuelle, Chenard, Marie-Pierre, Dauplat, Marie-Mélanie, Delrée, Paul, Fleury, Clémence, Garbar, Christian, Ghnassia, Jean-Pierre, Haudebourg, Juliette, MacGrogan, Gaëtan, Mathieu, Marie-Christine, Michenet, Patrick, Penault-Llorca, Frédérique, Poulet, Bruno, Robin, Yves, Roger, Pascal, Russ, Elisabeth, Treilleux, Isabelle, Valent, Alexander, Verriele, Véronique, Vincent-Salomon, Anne, Arnould, Laurent, Lacroix-Triki, Magali, Institut du Cancer de Montpellier (ICM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Hôpital René HUGUENIN (Saint-Cloud), Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel), Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Jean Godinot [Reims], Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de Hautepierre [Strasbourg], Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Institut de Pathologie et Génétique [Gosselies] (I.P.G.), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Validation et identification de nouvelles cibles en oncologie (VINCO), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biologie et pathologie médicales [Gustave Roussy], Institut Gustave Roussy (IGR), Centre Hospitalier Régional d'Orléans (CHRO), Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, Université de Montpellier (UM), Département d'anatomopathologie, biopathologie, Centre Léon Bérard [Lyon], Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), Institut Curie [Paris], Université Lumière - Lyon 2 - UFR de Sciences économiques et de gestion (UL2 UFR SEG), Université Lumière - Lyon 2 (UL2), Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Lille Nord de France (COMUE)-UNICANCER, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CRLCC Institut Claudius Regaud, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Pathology Bratislava, NUT a RCH, Service d'Anatomie Pathologique Générale, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service d'anatomo-pathologie, Centre Jean Perrin, Pathology Department, CRLCC Paul Strauss, Laboratoire d'Anatomo-Pathologie, Hôpital Pasteur [Nice] (CHU), Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pathologie, CHU Orléans, CRLCC Jean Perrin, Calculateurs Parallèles (CALCPAR), Institut de Recherche en Informatique et Systèmes Aléatoires (IRISA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-INRIA Rennes, Institut National de Recherche en Informatique et en Automatique (Inria), Institut de cancérologie de l'Ouest - Paul Papin (ICO - Paul Papin), Department of Tumor Biology, Institut Curie, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Neoplasm, Residual, Tissue sample, Recommandations, [SDV]Life Sciences [q-bio], Biopsy, Prélèvement, Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Guidelines, Medical Records, Réponse pathologique, Specimen Handling, Breast cancer, Biomarkers, Tumor, Humans, Néoadjuvant, Breast, Cancer du sein, Microscopy, Sentinel Lymph Node Biopsy, Prognosis, Neoadjuvant Therapy, Tumor Burden, Treatment Outcome, Chemotherapy, Adjuvant, Female, France, Lymph Nodes, Drug Screening Assays, Antitumor, Pathological response
Abstract: International audience; Neoadjuvant therapy is an increasing treatment option in the management of breast cancer. The tumor response to neoadjuvant therapy, especially the pathological complete response, is a validated endpoint frequently used in clinical trials. However, there is still a lack of standardization for the surgical specimen management in the neoadjuvant setting. This leads to heterogeneity in the specimen handling and might lead to significant bias for the prognostic assessment of patients or in clinical trials. The GEFPICS group, composed of expert breast cancer pathologists, herein presents guidelines for the management of breast and axillary specimen before treatment (management of biopsy, items of the pathological report) and after neoadjuvant therapy (specimen handling, histological assessment of response, items of the pathological report and response grading systems).
Published: 2018

46. Ustekinumab for skin reactions associated with anti‐tumor necrosis factor‐α agents in patients with inflammatory bowel diseases: A single‐center retrospective study

Author: Hedia Brixi, Philippe Bernard, Khaled Ezzedine, Guillaume Cadiot, L. Visseaux, Ziad Reguiai, Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: Adult, Male, medicine.medical_specialty, Necrosis, Cutaneous Polyarteritis Nodosa, Injections, Subcutaneous, Dermatology, Single Center, Inflammatory bowel disease, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Gastrointestinal Agents, Ustekinumab, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, integumentary system, business.industry, Tumor Necrosis Factor-alpha, Retrospective cohort study, General Medicine, Off-Label Use, Alopecia areata, Middle Aged, medicine.disease, Inflammatory Bowel Diseases, Ulcerative colitis, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Dermatologic Agents, Drug Eruptions, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: Anti-tumor necrosis factor (TNF)-α agents may induce skin reactions, in particular in patients with inflammatory bowel diseases (IBD). The objective of this study was to determine the efficacy of ustekinumab in these patients. IBD patients facing therapeutic issues because of cutaneous reactions or tolerance issues, consequently treated with ustekinumab in our department, were included. Retrospective review of case records and clinical photographs was carried out. Twenty-six patients were included. Twenty-three patients were treated for Crohn's disease and three for ulcerative colitis. Fourteen patients presented psoriasiform lesions, nine eczematiform lesions, four anaphylactoid reactions, two alopecia areata-like lesions, one injection-site reaction, one cutaneous polyarteritis nodosa and five other skin reactions. Most of them resolved under ustekinumab. In detail, eczematiform lesions completely resolved in all cases, psoriasiform lesions completely resolved in 12 cases (85.7%) and had partial response in two cases (14.3%). Two cases of alopecia areata showed complete response (complete hair regrowth). Fourteen patients showed complete digestive response, 10 patients partial digestive response (seven of which needed IBD treatment optimization) and only two failure. In conclusion, ustekinumab is a drug of choice in patients with IBD who cannot tolerate TNF blockers.
Published: 2018

47. Matrix remodelling and MMP expression/activation are associated with hidradenitis suppurativa skin inflammation

Author: Sébastien Le Jan, C. Muller, Frank Antonicelli, Philippe Bernard, J. Sanchez, Anne Durlach, Y. Renard, C. François, Ziad Reguiai, Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), and Service de Chirurgie Digestive [CHU Reims]
Subjects: 0301 basic medicine, Adult, Male, Pathology, medicine.medical_specialty, skin architecture, Inflammasomes, Biopsy, Cell Culture Techniques, Inflammation, Dermatology, Matrix metalloproteinase, Biochemistry, Gene Expression Regulation, Enzymologic, Extracellular matrix, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, NLR Family, Pyrin Domain-Containing 3 Protein, Medicine, Humans, Hidradenitis suppurativa, Molecular Biology, Acne, Cells, Cultured, Skin, biology, medicine.diagnostic_test, integumentary system, business.industry, Caspase 1, Middle Aged, medicine.disease, Hair follicle, Extracellular Matrix, Hidradenitis Suppurativa, 030104 developmental biology, medicine.anatomical_structure, Matrix Metalloproteinase 9, Skin biopsy, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytokines, Matrix Metalloproteinase 2, Female, medicine.symptom, business, Elastin
Abstract: International audience; Hidradenitis suppurativa/acne inversa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease of the hair follicle, associated with considerable tissue remodelling. Although abnormal cytokine expression was detected both in perilesional and in uninvolved skin, up to now there is no model allowing a better understanding of the implicit inflammatory mechanisms in HS. The aim of this study was to investigate the inflammatory response in HS skin by mean of an ex vivo model culture. To that purpose, nine skin biopsy specimens from patients suffering from HS and controls were cultured up to 4 days. Microscopy imaging investigations showed variations of collagen I and III organization, and an increase in elastin fibres fragmentation in HS skin after 4 days of culture. The HS matrix structure remodelling was associated with high level of MMP-2 and MMP-9 in HS lesional skin. After 4 days of culture, the MMP expression in HS perilesional skin reached the level observed in HS lesional skin. Concomitantly, an increase in IL-1β concentration was observed in all skin samples after 4 days of culture, although IL-1β concentrations remained significantly higher in HS lesional skin as compared with control skin. Meanwhile, neither IL-17 concentrations nor the inflammasome components NLRP3 and caspase-1 varied. Thus, our HS skin model culture showed that MMP-induced matrix alteration could participate in HS inflammation by releasing biological active peptides and inflammatory factors from the extracellular matrix (ECM), and open new opportunities to investigate the regulation of the inflammatory mechanism associated with HS.
Published: 2018

48. Chemotherapy treatment induces an increase of autophagy in the luminal breast cancer cell MCF7, but not in the triple-negative MDA-MB231

Author: Jérôme Giustiniani, Yacine Merrouche, Christian Garbar, Corinne Mascaux, Armand Bensussan, Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), Université de Reims Champagne-Ardenne (URCA), Institut Jean Godinot [Reims], UNICANCER, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Pommier, Arnaud, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
Subjects: 0301 basic medicine, Oncology, medicine.medical_specialty, Science, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Gene Expression, Antineoplastic Agents, Breast Neoplasms, Triple Negative Breast Neoplasms, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Article, 03 medical and health sciences, Basal (phylogenetics), Breast cancer, Cell Line, Tumor, Internal medicine, Autophagy, Biomarkers, Tumor, Humans, Medicine, skin and connective tissue diseases, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, neoplasms, Cells, Cultured, MUC1, Chemotherapy, Multidisciplinary, biology, business.industry, medicine.disease, Immunohistochemistry, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, Drug Resistance, Neoplasm, Cell culture, MCF-7 Cells, biology.protein, Female, Antibody, business
Abstract: Autophagy is one of the chemotherapy resistance mechanisms in breast cancer. The aim of this study was to determine the level of recruitment of the autophagy pathway in the triple-negative breast cancer (TNBC) cell line MDA-MB231 compared with that in the control luminal breast cancer cell line MCF7 before and after treatment with chemotherapy drugs. Furthermore, we investigated the relationship between autophagy and EGFR, MUC1 and IL17-receptors as activators of autophagy. Immunohistochemistry was performed in cell culture blocks using LC3b, MUC1-C, EGFR, IL17A, IL17-RA and IL17-RB antibodies. We found that the basal autophagy level in MDA-MB231 was high, whereas it was low in MCF7. However, in contrast to MDA-MB231, the autophagy level was increased in MCF7 upon treatment with chemotherapy agents. Interestingly, we observed that the expression levels of MUC1-C, EGFR, IL17-RA, and IL17-RB were not modified by the same treatments. Furthermore, the chemotherapy treatments did not increase autophagy in TNBC cells without affecting the expression levels of MUC1-C, EGFR, IL17-RA or IL17-RB.
Published: 2017

49. Association of Transient Palmoplantar Keratoderma With Clinical and Immunologic Characteristics of Bullous Pemphigoid

Author: Frank Antonicelli, Céline Muller, Philippe Bernard, Nina Antonicelli, Manuelle Viguier, J. Plée, Claire Duretz, Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC), and Université de Reims Champagne-Ardenne (URCA)
Subjects: Male, medicine.medical_specialty, Pemphigoid, Comorbidity, Dermatology, Autoantigens, Risk Assessment, Severity of Illness Index, Gastroenterology, Cohort Studies, Tertiary Care Centers, 030207 dermatology & venereal diseases, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Keratoderma, Palmoplantar, Internal medicine, Psoriasis, Pemphigoid, Bullous, Severity of illness, medicine, Humans, Clinical significance, Keratoderma, ComputingMilieux_MISCELLANEOUS, Aged, Autoantibodies, Retrospective Studies, business.industry, Brief Report, Incidence, Interleukin-17, Age Factors, Middle Aged, Non-Fibrillar Collagens, Prognosis, medicine.disease, Pathophysiology, 3. Good health, Palmoplantar keratoderma, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, France, Bullous pemphigoid, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Biomarkers
Abstract: Importance Development of transient palmoplantar keratoderma (PPK) with bullous pemphigoid (BP) has only been described in 2 isolated case reports. The clinical significance and the pathophysiologic mechanisms of this association are unknown. Objective To examine the clinical characteristics and immunological profile of patients with BP who develop transient PPK and analyze therapeutic options and outcomes. Design, Setting, and Participants In this case series, patients with BP who developed acquired, transient PPK, and were treated at a single institution from January 1, 2015, through December 31, 2017, were studied. Main Outcomes and Measures Clinical and immunological activity of BP, treatment administrated before and after PPK appearance, and patient outcomes. Results Six patients with BP and transient PPK were identified and included in the study. There were 5 women and 1 man with a mean age of 72 years. At baseline, all patients had a generalized, multibullous BP and high serum anti-BP180 antibodies (mean, 130 U/mL; range, 73-150), whereas anti-BP230 antibodies were elevated in only 1 case. The PPK appeared a mean 6.2 (range, 2-12) months after BP diagnosis, following a prolonged period of disease activity with recurrent flares. When the PPK occurred, BP was uncontrolled on therapy (mean Bullous Pemphigoid Disease Activity Index [BPDAI] score, 57; range, 34-105; mean anti-BP180 antibodies titer, 122 U/mL; range, 81-150). On administration of additional systemic immunosuppressive therapies, the PPK healed progressively in a mean 4.3 months (range, 2-9), along with BP clinical remission in 4 of 6 patients. No relationship was found between PPK occurrence and anti-BP180/230 antibodies profiles. In contrast, blister fluids collected at the time of PPK displayed a much higher level of interleukin 1β (IL-1β) compared with those collected in the absence of PKK. Expression of IL-17A, IL-17F, and IL-22 was also enhanced in the blister fluid of patients with BP who had PPK Conclusions and Relevance To our knowledge, this is the first report of 6 cases of BP with transient PPK with extensive immunological investigation. The PPK appeared after a prolonged period of clinical BP activity punctuated with recurrent relapses, was transient, and healed after BP control with additional immunosuppressive therapy. Enhanced expression of a particular cytokine panel in the blister fluid at time of PPK could support keratinocyte proliferation as described in patients with psoriasis. Transient PPK could represent a clinical marker of severe, treatment-resistant BP.
Published: 2019

50. Bullous pemphigoid outcome is associated with CXCL10-induced matrix metalloproteinase 9 secretion from monocytes and neutrophils but not lymphocytes

Author: Frank Antonicelli, Sébastien Le Jan, Guy Haegeman, Meriem Riani, Anne Durlach, Richard Le Naour, J. Plée, Philippe Bernard, Genetique des Maladies Vasculaires, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité Adaptative et Fonctionnalité des Barrières Biologiques - EA 4683 (IMAB), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV), Department of Physiology, Universiteit Gent = Ghent University [Belgium] (UGENT), Direction de la recherche, Société des accumulateurs fixes et de traction (SAFT), Université de Reims Champagne-Ardenne (URCA), Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), and Immuno-Régulation dans les Maladies Auto-Immunes Inflammatoires et le Cancer - EA 7509 (IRMAIC)
Subjects: 0301 basic medicine, Male, Chemokine, Neutrophils, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Monocytes, 030207 dermatology & venereal diseases, 0302 clinical medicine, Glucocorticoid receptor, Blister, Pemphigoid, Bullous, Immunology and Allergy, Lymphocytes, skin and connective tissue diseases, Cells, Cultured, selective glucocorticoid receptor activator, Skin, Aged, 80 and over, medicine.diagnostic_test, biology, integumentary system, CXCL10, autoimmunity, Middle Aged, 3. Good health, Cytokine, Matrix Metalloproteinase 9, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Bullous pemphigoid, Immunology, Cell Line, 03 medical and health sciences, Immune system, medicine, Humans, Aged, Autoimmune disease, compound A, business.industry, medicine.disease, Chemokine CXCL10, 030104 developmental biology, inflammation, Skin biopsy, biology.protein, business
Abstract: International audience; Background: The outcome of bullous pemphigoid (BP), the most frequent autoimmune skin-blistering disease, involves matrix metalloproteinase 9 (MMP-9), IL-17, and IL-23 release from infiltrated inflammatory cells. The chemokine CXCL10 has been associated with several autoimmune diseases, but its participation in BP pathophysiology still needs to be clarified. Objective: We sought to assess whether BP outcome was associated with different CXCL10 levels and to evaluate the contribution of CXCL10 to the described cytokine/protease inflammatory loop associated with disease outcome. Methods: Skin biopsy specimens (n 5 16), serum (n 5 114), blister fluid (n 5 23), and primary inflammatory cells from patients with BP were used to investigate CXCL10 expression and function. Results: At baseline, both resident cells, such as keratinocytes and fibroblasts, and infiltrating immune cells expressed CXCL10 at lesional sites in skin of patients with BP. CXCL10 levels were higher in blister fluid (P < .0001) and serum (P < .005) from patients with BP than in serum from age-and sex-matched control subjects (n 5 34). Furthermore, CXCL10 serum levels increased at day 60 only in patients who relapsed within the first year of treatment (n 5 33, P < .005). Interestingly, CXCL10 expression could be upregulated by itself and IL-17 in inflammatory cells. Notably, neutrophils and monocytes from patients with BP, but not lymphocytes, responded to CXCL10 by increasing MMP-9 secretion through the activation of extracellular signal-regulated kinase 1/2, p38, phosphoinositide-3 kinase signaling pathways. Finally, CXCL10-increased MMP-9 secretion was inhibited by methylprednisolone and also by compound A, a novel nonsteroidal glucocorticoid receptor ligand. Conclusion: We showed that increased levels of inflammatory biomarkers in patients with BP, such as CXCL10, favor neutrophil-and monocyte-associated MMP-9 release and disease relapse and opened new therapeutic horizons in patients with this autoimmune disease.
Published: 2016

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