1. Type I interferon response and vascular alteration in chilblain‐like lesions during the COVID‐19 outbreak*
- Author
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Jérôme Hadjadj, Bruno Charbit, Djaouida Bengoufa, A. Philippe, Laura Barnabei, Olivier Schwartz, Coralie L. Guerin, Léa Jaume, Hervé Bachelez, Darragh Duffy, David M. Smadja, Jean-David Bouaziz, Nicolas Gendron, A. Calugareanu, B. Joly, Sonia Meynier, Martine Bagot, Saint-Louis Core, Frédéric Rieux-Laucat, Jérôme LeGoff, H. Le Buanec, Marisa Battistella, S. Maylin, Nader Yatim, C. Delaugerre, V. Siguret, Richard Chocron, Charles Cassius, L. Frumholtz, Ludivine Grzelak, Nikaïa Smith, Université de Paris, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Hopital Saint-Louis [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 Paris Cité (UPCité), Immunogenetics of pediatric autoimmune diseases (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), Hôpital Cochin [AP-HP], 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Immunologie Translationnelle - Translational Immunology lab, Institut Pasteur [Paris] (IP), Cytometrie et Biomarqueurs – Cytometry and Biomarkers (UTechS CB), Innovations thérapeutiques en hémostase = Innovative Therapies in Haemostasis (IThEM - U1140), Institut Curie [Paris], Hôpital Lariboisière-Fernand-Widal [APHP], Recherche clinique appliquée à l'hématologie (URP_3518), Université Paris Cité (UPCité), Genetic skin diseases : from disease mechanism to therapies (Equipe Inserm U1163), Fondation Alain Carpentier - (Centre Médical International) [Paris] (FAC - CMI), 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), The study was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM) and by a government grant managed by the Agence National de la Recherche as part of the ‘Investment for the Future’ programme (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01, Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010), grants from the Agence National de la Recherche (ANR-flash Covid19 ‘AIROCovid’ to F.R.L.) and by the FAST Foundation (French Friends of Sheba Tel Hashomer Hospital). J.H. was a recipient of an INSERM ‘poste d’acceuil’ programme, and an Institut Imagine MD-PhD fellowship programme supported by the Fondation Bettencourt Schueller. L.B. was a recipient of an Imagine Institute PhD international programme supported by the Fondation Bettencourt Schueller. S. Meynier was a recipient of an INSERM and Institut Imagine postdoctoral programme supported by the Fondation pour la Recherche Médicale (FRM no. SPF20170938825)., ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), and ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018)
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0303 health sciences ,business.industry ,Angiogenesis ,[SDV]Life Sciences [q-bio] ,Dermatology ,Gene signature ,medicine.disease ,Endothelial progenitor cell ,Pathophysiology ,3. Good health ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,immune system diseases ,hemic and lymphatic diseases ,Immunology ,Medicine ,Endothelial dysfunction ,business ,Chilblains ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Anti-neutrophil cytoplasmic antibody - Abstract
International audience; BackgroundThe outbreak of chilblain-like lesions (CLL) during the COVID-19 pandemic has been reported extensively, potentially related to SARS-CoV-2 infection, yet its underlying pathophysiology is unclear.ObjectivesTo study skin and blood endothelial and immune system activation in CLL in comparison with healthy controls and seasonal chilblains (SC), defined as cold-induced sporadic chilblains occurring during 2015 and 2019 with exclusion of chilblain lupus.MethodsThis observational study was conducted during 9–16 April 2020 at Saint-Louis Hospital, Paris, France. All patients referred with CLL seen during this period of the COVID-19 pandemic were included in this study. We excluded patients with a history of chilblains or chilblain lupus. Fifty patients were included.ResultsHistological patterns were similar and transcriptomic signatures overlapped in both the CLL and SC groups, with type I interferon polarization and a cytotoxic–natural killer gene signature. CLL were characterized by higher IgA tissue deposition and more significant transcriptomic activation of complement and angiogenesis factors compared with SC. We observed in CLL a systemic immune response associated with IgA antineutrophil cytoplasmic antibodies in 73% of patients, and elevated type I interferon blood signature in comparison with healthy controls. Finally, using blood biomarkers related to endothelial dysfunction and activation, and to angiogenesis or endothelial progenitor cell mobilization, we confirmed endothelial dysfunction in CLL.ConclusionsOur findings support an activation loop in the skin in CLL associated with endothelial alteration and immune infiltration of cytotoxic and type I IFN-polarized cells leading to clinical manifestations.
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- 2021
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