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1. The role of complement in kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

Alberici, Federico, Antonucci, Luca, Avcin, Tadej, Bagga, Arvind, Bajema, Ingeborg M., Blasco, Miquel, Chauvet, Sophie, Cook, H. Terence, Cravedi, Paolo, Dragon-Durey, Marie-Agnès, Fischer, Lauren, Fogo, Agnes B., Frazer-Abel, Ashley, Frémeaux-Bacchi, Véronique, Görlich, Nina, Haas, Mark, Humphreys, Alister, Jha, Vivekanand, Jauhal, Arenn, Kavanagh, David, Kronbichler, Andreas, Lafayette, Richard A., Lanning, Lynne D., Lemaire, Mathieu, Le Quintrec, Moglie, Licht, Christoph, Liew, Adrian, McAdoo, Steve, Medjeral-Thomas, Nicholas R., Meroni, Pier Luigi, Morelle, Johann, Nester, Carla M., Praga, Manuel, Ramachandran, Raja, Reich, Heather N., Remuzzi, Giuseppe, Rodríguez de Córdoba, Santiago, Robinson, Gary, Ronco, Pierre, Rossing, Peter, Salant, David J., Sethi, Sanjeev, Silkjaer, Marianne, Song, Wen-chao, Spoleti, Fabrizio, Taylor, Ronald P., van de Kar, Nicole C.A.J., van Kooten, Cees, Woodward, Len, Zhang, Yuzhou, Zipfel, Peter F., Zuccato, Marco, Vivarelli, Marina, Barratt, Jonathan, Beck, Laurence H., Jr., Fakhouri, Fadi, Gale, Daniel P., Goicoechea de Jorge, Elena, Mosca, Marta, Noris, Marina, Pickering, Matthew C., Susztak, Katalin, Thurman, Joshua M., Cheung, Michael, King, Jennifer M., Jadoul, Michel, Winkelmayer, Wolfgang C., and Smith, Richard J.H.

Published
2024
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3. Genetic Diagnosis Guides Treatment of Autoimmune Enteropathy

Author

Charbit-Henrion, Fabienne, Haas, Manon, Chaussade, Stanislas, Cellier, Christophe, Cerf-Bensussan, Nadine, Malamut, Georgia, Khater, Sherine, Khiat, Anis, Cording, Sascha, Parlato, Marianna, Dragon-Durey, Marie-Agnès, Beuvon, Frédéric, Brousse, Nicole, Terris, Benoît, Picard, Capucine, Fusaro, Mathieu, Rieux-Laucat, Frédéric, Stolzenberg, Marie-Claude, Jannot, Anne-Sophie, Mathian, Alexis, Allez, Matthieu, Malphettes, Marion, Fieschi, Claire, Aubourg, Alexandre, Zallot, Camille, Roblin, Xavier, Abitbol, Vered, Belle, Arthur, Wils, Pauline, Cheminant, Morgane, Matysiak-Budnik, Tamara, Vuitton, Lucine, Pouderoux, Philippe, Abramowitz, Laurent, Castelle, Martin, Suarez, Felipe, Hermine, Olivier, Ruemmele, Frank, and Mouthon, Luc

Published
2023
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4. The Role of Complement in Kidney Disease: Conclusions From a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference

Author

Vivarelli, Marina, primary, Barratt, Jonathan, additional, Beck, Laurence H., additional, Fakhouri, Fadi, additional, Gale, Daniel P., additional, de Jorge, Elena Goicoechea, additional, Mosca, Marta, additional, Noris, Marina, additional, Pickering, Matthew C., additional, Susztak, Katalin, additional, Thurman, Joshua M., additional, Cheung, Michael, additional, King, Jennifer M., additional, Jadoul, Michel, additional, Winkelmayer, Wolfgang C., additional, Smith, Richard J.H., additional, Alberici, Federico, additional, Antonucci, Luca, additional, Avcin, Tadej, additional, Bagga, Arvind, additional, Bajema, Ingeborg M., additional, Blasco, Miquel, additional, Chauvet, Sophie, additional, Cook, H. Terence, additional, Cravedi, Paolo, additional, Dragon-Durey, Marie-Agnès, additional, Fischer, Lauren, additional, Fogo, Agnes B., additional, Frazer-Abel, Ashley, additional, Frémeaux-Bacchi, Véronique, additional, Görlich, Nina, additional, Haas, Mark, additional, Humphreys, Alister, additional, Jha, Vivekanand, additional, Jauhal, Arenn, additional, Kavanagh, David, additional, Kronbichler, Andreas, additional, Lafayette, Richard A., additional, Lanning, Lynne D., additional, Lemaire, Mathieu, additional, Le Quintrec, Moglie, additional, Licht, Christoph, additional, Liew, Adrian, additional, McAdoo, Steve, additional, Medjeral-Thomas, Nicholas R., additional, Meroni, Pier Luigi, additional, Morelle, Johann, additional, Nester, Carla M., additional, Praga, Manuel, additional, Ramachandran, Raja, additional, Reich, Heather N., additional, Remuzzi, Giuseppe, additional, Rodríguez de Córdoba, Santiago, additional, Robinson, Gary, additional, Ronco, Pierre, additional, Rossing, Peter, additional, Salant, David J., additional, Sethi, Sanjeev, additional, Silkjaer, Marianne, additional, Song, Wen-chao, additional, Spoleti, Fabrizio, additional, Taylor, Ronald P., additional, van de Kar, Nicole C.A. J., additional, van Kooten, Cees, additional, Woodward, Len, additional, Zhang, Yuzhou, additional, Zipfel, Peter F., additional, and Zuccato, Marco, additional

Published
2024
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5. C5 nephritic factors drive the biological phenotype of C3 glomerulopathies

Author

Marinozzi, Maria-Chiara, Chauvet, Sophie, Le Quintrec, Moglie, Mignotet, Morgane, Petitprez, Florent, Legendre, Christophe, Cailliez, Mathilde, Deschenes, Georges, Fischbach, Michel, Karras, Alexandre, Nobili, Francois, Pietrement, Christine, Dragon-Durey, Marie-Agnes, Fakhouri, Fadi, Roumenina, Lubka T., and Fremeaux-Bacchi, Veronique

Published
2017
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7. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

Author

Alpers, Charlie E., Appel, Gerald B., Ardissino, Gianluigi, Ariceta, Gema, Arici, Mustafa, Bagga, Arvind, Bajema, Ingeborg M., Blasco, Miguel, Burke, Linda, Cairns, Thomas D., Carratala, Mireya, D'Agati, Vivette D., Daha, Mohamed R., De Vriese, An S., Dragon-Durey, Marie-Agnès, Fogo, Agnes B., Galbusera, Miriam, Gale, Daniel P., Haller, Hermann, Johnson, Sally, Józsi, Mihály, Karpman, Diana, Lanning, Lynne, Le Quintrec, Moglie, Licht, Christoph, Loirat, Chantal, Monfort, Francisco, Morgan, B. Paul, Noël, Laure-Hélène, O'Shaughnessy, Michelle M., Rabant, Marion, Rondeau, Eric, Ruggenenti, Piero, Sheerin, Neil S., Smith, Jenna, Spoleti, Fabrizio, Thurman, Joshua M., van de Kar, Nicole C.A.J., Vivarelli, Marina, Zipfel, Peter F., Goodship, Timothy H.J., Cook, H. Terence, Fakhouri, Fadi, Fervenza, Fernando C., Frémeaux-Bacchi, Véronique, Kavanagh, David, Nester, Carla M., Noris, Marina, Pickering, Matthew C., Rodríguez de Córdoba, Santiago, Roumenina, Lubka T., Sethi, Sanjeev, and Smith, Richard J.H.

Published
2017
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10. Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children

Author

Sinha, Aditi, Gulati, Ashima, Saini, Savita, Blanc, Caroline, Gupta, Aarti, Gurjar, Bahadur Singh, Saini, Himanshi, Kotresh, Shambhuprasad T., Ali, Uma, Bhatia, Divya, Ohri, Alpana, Kumar, Manish, Agarwal, Indira, Gulati, Sanjeev, Anand, Kanav, Vijayakumar, M., Sinha, Rajiv, Sethi, Sidharth, Salmona, Maud, George, Anna, Bal, Vineeta, Singh, Geetika, Dinda, Amit K., Hari, Pankaj, Rath, Satyajit, Dragon-Durey, Marie-Agnes, Bagga, Arvind, and for the Indian HUS Registry

Published
2014
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13. Repository of intra-and inter-run variations of quantitative autoantibody assays: A European multicenter study

Author

Dragon-Durey, Marie-Agnès, Bizzaro, Nicola, Senant, Marie, Andreeva, Hristina, Bogdanos, Dimitrios P., Bonroy, Carolien, Bossuyt, Xavier, Eriksson, Catharina, Fabien, Nicole, Heijnen, Ingmar, Herold, Manfred, Musset, Lucile, Kuhi, Liisa, Lopez-Hoyos, Marcos, Berki, Tímea, Roozendaal, Caroline, Sack, Ulrich, Sundic, Tatjana, Taylor, Lorna, Kuna, Andrea Tesija, Damoiseaux, Jan, Dragon-Durey, Marie-Agnès, Bizzaro, Nicola, Senant, Marie, Andreeva, Hristina, Bogdanos, Dimitrios P., Bonroy, Carolien, Bossuyt, Xavier, Eriksson, Catharina, Fabien, Nicole, Heijnen, Ingmar, Herold, Manfred, Musset, Lucile, Kuhi, Liisa, Lopez-Hoyos, Marcos, Berki, Tímea, Roozendaal, Caroline, Sack, Ulrich, Sundic, Tatjana, Taylor, Lorna, Kuna, Andrea Tesija, and Damoiseaux, Jan

Abstract

No reference data are available on repositories to measure precision of autoantibody assays. The scope of this study was to document inter-and intra-run variations of quantitative autoantibody assays based on a real-world large international data set. Members of the European Autoimmunity Standardisation Initiative (EASI) group collected the data of intra-and inter-run variability obtained with assays quantifying 15 different autoantibodies in voluntary participating laboratories from their country. We analyzed the impact on the assay performances of the type of immunoassay, the number of measurements used to calculate the coefficient of variation (CVs), the nature and the autoantibody level of the internal quality control (IQC). Data were obtained from 64 laboratories from 15 European countries between February and October 2021. We analyzed 686 and 1,331 values of intra-and inter-run CVs, respectively. Both CVs were significantly dependent on: The method of immunoassay, the level of IQC with higher imprecision observed when the antibody levels were lower than 2-fold the threshold for positivity, and the nature of the IQC with commercial IQCs having lower CVs than patients-derived IQCs. Our analyses also show that the type of autoantibody has low impact on the assay' performances and that 15 measurements are sufficient to establish reliable intra-and inter-run variations. This study provides for the first time an international repository yielding values of intra-and inter-run variation for quantitative autoantibody assays. These data could be useful for ISO 15189 accreditation requirements and will allow clinical diagnostic laboratories to assure quality of patient results.

Published
2022
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15. Hyperfunctional C3 convertase leads to complement deposition on endothelial cells and contributes to atypical hemolytic uremic syndrome

Author

Roumenina, Lubka T., Jablonski, Mathieu, Hue, Christophe, Blouin, Jacques, Dimitrov, Jordan D., Dragon-Durey, Marie-Agnes, Cayla, Mathieu, Fridman, Wolf H., Macher, Marie-Alice, Ribes, David, Moulonguet, Luc, Rostaing, Lionel, Satchell, Simon C., Mathieson, Peter W., Sautes-Fridman, Catherine, Loirat, Chantal, Regnier, Catherine H., Halbwachs-Mecarelli, Lise, and Fremeaux-Bacchi, Veronique

Published
2009
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16. Lupus Anticoagulant Single Positivity During the Acute Phase of COVID‐19 Is Not Associated With Venous Thromboembolism or In‐Hospital Mortality

Author

Gendron, Nicolas, primary, Dragon‐Durey, Marie‐Agnès, additional, Chocron, Richard, additional, Darnige, Luc, additional, Jourdi, Georges, additional, Philippe, Aurélien, additional, Chenevier‐Gobeaux, Camille, additional, Hadjadj, Jérôme, additional, Duchemin, Jérôme, additional, Khider, Lina, additional, Yatim, Nader, additional, Goudot, Guillaume, additional, Krzisch, Daphné, additional, Debuc, Benjamin, additional, Mauge, Laetitia, additional, Levavasseur, Françoise, additional, Pene, Frédéric, additional, Boussier, Jeremy, additional, Sourdeau, Elise, additional, Brichet, Julie, additional, Ochat, Nadège, additional, Goulvestre, Claire, additional, Peronino, Christophe, additional, Szwebel, Tali‐Anne, additional, Pages, Franck, additional, Gaussem, Pascale, additional, Samama, Charles‐Marc, additional, Cheurfa, Cherifa, additional, Planquette, Benjamin, additional, Sanchez, Olivier, additional, Diehl, Jean‐Luc, additional, Mirault, Tristan, additional, Fontenay, Michaela, additional, Terrier, Benjamin, additional, and Smadja, David M., additional

Published
2021
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17. Differential association between inflammatory cytokines and multiorgan dysfunction in COVID-19 patients with obesity

Author

Dragon-Durey, Marie-Agnès, Chen, Xiaoyi, Kirilovsky, Amos, Ben Hamouda, Nadine, El Sissy, Carine, Russick, Jules, Charpentier, Etienne, Binois, Yannick, Marliot, Florence, Meylan, Maxime, Granier, Clémence, Pere, Hélène, Saldmann, Antonin, Rance, Bastien, Jannot, Anne Sophie, Baron, Stéphanie, Chebbi, Mouna, Fayol, Antoine, Josseaume, Nathalie, Rives-Lange, Claire, Tharaux, Pierre-Louis, Cholley, Bernard, Diehl, Jean-Luc, Arlet, Jean-Benoît, Azizi, Michel, Karras, Alexandre, Czernichow, Sébastien, Smadja, David M., Hulot, Jean-Sébastien, Cremer, Isabelle, Tartour, Eric, Mousseaux, Elie, Pagès, Franck, 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), 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 de Paris (UP), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Innovations thérapeutiques en hémostase (IThEM - U1140), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), CIC - HEGP (CIC 1418), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
RNA viruses, Male, Viral Diseases, Physiology, Coronaviruses, [SDV]Life Sciences [q-bio], Severity of Illness Index, Body Mass Index, Diagnostic Radiology, Medical Conditions, Immune Physiology, Medicine and Health Sciences, Prospective Studies, Immune Response, Tomography, Lung, Pathology and laboratory medicine, Virus Testing, Innate Immune System, Radiology and Imaging, Medical microbiology, Middle Aged, Hospitalization, Intensive Care Units, Infectious Diseases, Physiological Parameters, Liver, Viruses, Cytokines, RNA, Viral, Medicine, Female, SARS CoV 2, Pathogens, Chemokines, Research Article, SARS coronavirus, Imaging Techniques, Science, Immunology, Neuroimaging, Research and Analysis Methods, Microbiology, Signs and Symptoms, Diagnostic Medicine, Humans, Obesity, Aged, Inflammation, SARS-CoV-2, Body Weight, Organisms, Viral pathogens, Biology and Life Sciences, COVID-19, Covid 19, Molecular Development, Microbial pathogens, Computed Axial Tomography, Immune System, Endothelium, Vascular, Clinical Medicine, Biomarkers, Developmental Biology, Neuroscience
Abstract

International audience; To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital organs' functions according to body mass index (BMI) categories. High-dimensional flow cytometric characterization of immune cell subsets was performed at admission, 30 systemic cytokines/chemokines levels were sequentially measured, thirteen endothelial markers were determined at admission and at the zenith of the cytokines. Computed tomography scans on admission were quantified for lung damage and hepatic steatosis (n = 23). Abnormal BMI (> 25) observed in 72.6% of patients, was associated with a higher rate of intensive care unit hospitalization (p = 0.044). SARS-CoV-2 RNAaemia, peripheral immune cell subsets and cytokines/chemokines were similar among BMI groups. A significant association between inflammatory cytokines and liver, renal, and endothelial dysfunctions was observed only in patients with obesity (BMI > 30). In contrast, early signs of lung damage (ground-glass opacity) correlated with Th1/M1/inflammatory cytokines only in normal weight patients. Later lesions of pulmonary consolidation correlated with BMI but were independent of cytokine levels. Our study reveals distinct physiopathological mechanisms associated with SARS-CoV-2 infection in patients with obesity that may have important clinical implications.

Published
2021
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18. Lupus anticoagulant single positivity at acute phase is not associated with venous thromboembolism or in‐hospital mortality in COVID‐19

Author

Gendron, Nicolas, Dragon‐Durey, Marie‐Agnès, Chocron, Richard, Darnige, Luc, Jourdi, Georges, Philippe, Aurélien, Chenevier‐Gobeaux, Camille, Hadjadj, Jérôme, Duchemin, Jérôme, Khider, Lina, Yatim, Nader, Goudot, Guillaume, Krzisch, Daphné, Debuc, Benjamin, Mauge, Laetitia, Levasseur, Françoise, Pene, Frédéric, Boussier, Jeremy, Sourdeau, Elise, Brichet, Julie, Ochat, Nadège, Goulvestre, Claire, Peronino, Christophe, Szwebel, Tali‐Anne, Pages, Franck, Gaussem, Pascale, Samama, Charles‐Marc, Cheurfa, Cherifa, Planquette, Benjamin, Sanchez, Olivier, Diehl, Jean‐Luc, Mirault, Tristan, Fontenay, Michaela, Terrier, Benjamin, and Smadja, David M.

Subjects
Aged, 80 and over, Male, Full Length, antiphospholipid antibodies, COVID-19, Venous Thromboembolism, Middle Aged, Prognosis, coagulopathy, Survival Rate, lupus anticoagulant, COVID‐19, inflammation, Risk Factors, Lupus Coagulation Inhibitor, Humans, Female, Hospital Mortality, Prospective Studies, thrombosis, Aged
Abstract

Introduction Antiphospholipid antibodies (APA) clinical relevance in COVID‐19 is controversial. We aimed to investigate the prevalence and prognostic value of conventional and non‐conventional APA in COVID‐19 patients. Methods This study was a multi‐centric, prospective observational French cohort of patients hospitalized for COVID‐19 suspicion. Results 249 patients were hospitalized for suspected COVID‐19, including 154 with confirmed COVID‐19 and 95 not confirmed. We found a significant increase in lupus anticoagulant (LA) positivity among COVID‐19 positive patients (60.9% versus 23.7% in non‐COVID19 patients, p

Published
2021

19. Immune Signature Linked to COVID-19 Severity: A SARS-Score for Personalized Medicine

Author

Russick, Jules, Foy, Pierre-Emmanuel, Josseaume, Nathalie, Meylan, Maxime, Hamouda, Nadine, Kirilovsky, Amos, Sissy, Carine, Tartour, Eric, Smadja, David, Karras, Alexandre, Hulot, Jean-Sébastien, Livrozet, Marine, Fayol, Antoine, Arlet, Jean-Benoit, Diehl, Jean-Luc, Dragon-Durey, Marie-Agnès, Pagès, Franck, Cremer, Isabelle, 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 de Paris (UP), 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), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), HAL-SU, Gestionnaire, 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), and 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)

Subjects
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, personalized medicine/personalized health care, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, COVID-19, score, immunologic profile, therapeutic strategy, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Abstract

International audience; SARS-CoV-2 infection leads to a highly variable clinical evolution, ranging from asymptomatic to severe disease with acute respiratory distress syndrome, requiring intensive care units (ICU) admission. The optimal management of hospitalized patients has become a worldwide concern and identification of immune biomarkers predictive of the clinical outcome for hospitalized patients remains a major challenge. Immunophenotyping and transcriptomic analysis of hospitalized COVID-19 patients at admission allow identifying the two categories of patients. Inflammation, high neutrophil activation, dysfunctional monocytic response and a strongly impaired adaptive immune response was observed in patients who will experience the more severe form of the disease. This observation was validated in an independent cohort of patients. Using in silico analysis on drug signature database, we identify differential therapeutics that specifically correspond to each group of patients. From this signature, we propose a score—the SARS-Score—composed of easily quantifiable biomarkers, to classify hospitalized patients upon arrival to adapt treatment according to their immune profile.

Published
2021
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22. A First-in-Human Phase I Study of INVAC-1, an Optimized Human Telomerase DNA Vaccine in Patients with Advanced Solid Tumors

Author

Teixeira, Luis, primary, Medioni, Jacques, additional, Garibal, Julie, additional, Adotevi, Olivier, additional, Doucet, Ludovic, additional, Durey, Marie-Agnès Dragon, additional, Ghrieb, Zineb, additional, Kiladjian, Jean-Jacques, additional, Brizard, Mara, additional, Laheurte, Caroline, additional, Wehbe, Maria, additional, Pliquet, Elodie, additional, Escande, Marie, additional, Defrance, Rémy, additional, Culine, Stephane, additional, Oudard, Stephane, additional, Wain-Hobson, Simon, additional, Doppler, Valérie, additional, Huet, Thierry, additional, and Langlade-Demoyen, Pierre, additional

Published
2020
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23. Serum Gp96 is a chaperone of complement-C3 during graft-versus-host disease

Author

Seignez, Antoine, Joly, Anne-Laure, Chaumonnot, Killian, Hazoumé, Adonis, Sanka, Michel, Marcion, Guillaume, Boudesco, Christophe, Hammann, Arlette, Seigneuric, Renaud, Jégo, Gaetan, Ducoroy, Patrick, Delarue, Patrice, Senet, Patrick, Castilla-Llorente, Cristina, Solary, Eric, Durey, Marie-Agnès, Rubio, Marie-Thérèse, Hermine, Olivier, Kohli, Evelyne, Garrido, Carmen, Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), 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, Plate-forme Protéomique CLIPP - Clinical and Innovation Proteomic Platform [Dijon] (CLIPP), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM)-Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interdisciplinaire Carnot de Bourgogne [Dijon] (LICB), Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), Institut Gustave Roussy (IGR), Hématopoïèse normale et pathologique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Service d'Immunologie Clinique, Hôpital Européen Georges Pompidou, Paris, Université Paris Descartes - Paris 5 (UPD5), Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cytokines, hématopoïèse et réponse immune (CHRI), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Necker - Enfants Malades [AP-HP], Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Plate-forme Protéomique CLIPP - Clinical and Innovation Proteomic Platform [Dijon] ( CLIPP ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) ( FEMTO-ST ), Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ) -Université de Franche-Comté ( UFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Supérieure de Mécanique et des Microtechniques ( ENSMM ) -Université de Technologie de Belfort-Montbeliard ( UTBM ) -Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] ( ICMUB ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Interdisciplinaire Carnot de Bourgogne [Dijon] ( LICB ), Université de Technologie de Belfort-Montbeliard ( UTBM ) -Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Gustave Roussy ( IGR ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Gustave Roussy ( IGR ) -Université Paris-Sud - Paris 11 ( UP11 ), Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Bourgogne (UB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interdisciplinaire Carnot de Bourgogne (ICB), Université de Technologie de Belfort-Montbeliard (UTBM)-Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre de Recherche Saint-Antoine (UMRS893), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Moléculaire de l'Université de Bourgogne [Dijon] (ICMUB), Université de Bourgogne (UB)-Université de Technologie de Belfort-Montbeliard (UTBM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hématologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Inhibitor, Adolescent, Cell Transplantation, Shock-Protein Gp96, Graft vs Host Disease, Mice, Young Adult, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Animals, Humans, Gata-1, Erythropoiesis, Complement Activation, ComputingMilieux_MISCELLANEOUS, Component C3, Membrane Glycoproteins, Hematopoietic Stem Cell Transplantation, Complement C3, Middle Aged, Differentiation, [SDV.IMM]Life Sciences [q-bio]/Immunology, Therapy, Glycoprotein 96, In-Vivo, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Research Article, Molecular Chaperones
Abstract

International audience; Better identification of severe acute graft-versus-host disease (GvHD) may improve the outcome of this life-threatening complication of allogeneic hematopoietic stem cell transplantation. GvHD induces tissue damage and the release of damage-associated molecular pattern (DAMP) molecules. Here, we analyzed GvHD patients (n = 39) to show that serum heat shock protein glycoprotein 96 (Gp96) could be such a DAMP molecule. We demonstrate that serum Gp96 increases in gastrointestinal GvHD patients and its level correlates with disease severity. An increase in Gp96 serum level was also observed in a mouse model of acute GvHD. This model was used to identify complement C3 as a main partner of Gp96 in the serum. Our biolayer interferometry, yeast two-hybrid and in silico modeling data allowed us to determine that Gp96 binds to a complement C3 fragment encompassing amino acids 749-954, a functional complement C3 hot spot important for binding of different regulators. Accordingly, in vitro experiments with purified proteins demonstrate that Gp96 downregulates several complement C3 functions. Finally, experimental induction of GvHD in complement C3-deficient mice confirms the link between Gp96 and complement C3 in the serum and with the severity of the disease.

Published
2017
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24. Both Monoclonal and Polyclonal Immunoglobulin Contingents Mediate Complement Activation in Monoclonal Gammopathy Associated-C3 Glomerulopathy

Author

Chauvet, Sophie, primary, Roumenina, Lubka T., additional, Aucouturier, Pierre, additional, Marinozzi, Maria-Chiara, additional, Dragon-Durey, Marie-Agnès, additional, Karras, Alexandre, additional, Delmas, Yahsou, additional, Le Quintrec, Moglie, additional, Guerrot, Dominique, additional, Jourde-Chiche, Noémie, additional, Ribes, David, additional, Ronco, Pierre, additional, Bridoux, Frank, additional, and Fremeaux-Bacchi, Véronique, additional

Published
2018
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25. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

Author

Goodship, Timothy H.J., primary, Cook, H. Terence, additional, Fakhouri, Fadi, additional, Fervenza, Fernando C., additional, Frémeaux-Bacchi, Véronique, additional, Kavanagh, David, additional, Nester, Carla M., additional, Noris, Marina, additional, Pickering, Matthew C., additional, Rodríguez de Córdoba, Santiago, additional, Roumenina, Lubka T., additional, Sethi, Sanjeev, additional, Smith, Richard J.H., additional, Alpers, Charlie E., additional, Appel, Gerald B., additional, Ardissino, Gianluigi, additional, Ariceta, Gema, additional, Arici, Mustafa, additional, Bagga, Arvind, additional, Bajema, Ingeborg M., additional, Blasco, Miguel, additional, Burke, Linda, additional, Cairns, Thomas D., additional, Carratala, Mireya, additional, D'Agati, Vivette D., additional, Daha, Mohamed R., additional, De Vriese, An S., additional, Dragon-Durey, Marie-Agnès, additional, Fogo, Agnes B., additional, Galbusera, Miriam, additional, Gale, Daniel P., additional, Haller, Hermann, additional, Johnson, Sally, additional, Józsi, Mihály, additional, Karpman, Diana, additional, Lanning, Lynne, additional, Le Quintrec, Moglie, additional, Licht, Christoph, additional, Loirat, Chantal, additional, Monfort, Francisco, additional, Morgan, B. Paul, additional, Noël, Laure-Hélène, additional, O'Shaughnessy, Michelle M., additional, Rabant, Marion, additional, Rondeau, Eric, additional, Ruggenenti, Piero, additional, Sheerin, Neil S., additional, Smith, Jenna, additional, Spoleti, Fabrizio, additional, Thurman, Joshua M., additional, van de Kar, Nicole C.A.J., additional, Vivarelli, Marina, additional, and Zipfel, Peter F., additional

Published
2017
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26. Functional Characterization of Anti-C3bBb Autoantibodies and C3 Glomerulopathy Phenotype

Author

Roquigny, Julia, Meuleman, Marie-Sophie, El Sissy, Carine, Cailliez, Mathilde, Servais, Aude, Roussey, Gwenaelle, Baudouin, Véronique, Decramer, Stéphane, Nobili, François, Wynckel, Alain, Sellier Leclerc, Anne-Laure, Lapeyraque, Anne-Laure, Martins, Paula Vieira, Meri, Seppo, Dragon-Durey, Marie-Agnès, Chauvet, Sophie, and Frémeaux-Bacchi, Véronique

Published
2024
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28. Genetics and Outcome of Atypical Hemolytic Uremic Syndrome

Author

Fremeaux-Bacchi, Véronique, primary, Fakhouri, Fadi, additional, Garnier, Arnaud, additional, Bienaimé, Frank, additional, Dragon-Durey, Marie-Agnès, additional, Ngo, Stéphanie, additional, Moulin, Bruno, additional, Servais, Aude, additional, Provot, François, additional, Rostaing, Lionel, additional, Burtey, Stéphane, additional, Niaudet, Patrick, additional, Deschênes, Georges, additional, Lebranchu, Yvon, additional, Zuber, Julien, additional, and Loirat, Chantal, additional

Published
2013
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29. Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome

Author

Frémeaux-Bacchi, Veronique, Miller, Elizabeth C., Liszewski, M. Kathryn, Strain, Lisa, Blouin, Jacques, Brown, Alison L., Moghal, Nadeem, Kaplan, Bernard S., Weiss, Robert A., Lhotta, Karl, Kapur, Gaurav, Mattoo, Tej, Nivet, Hubert, Wong, William, Gie, Sophie, de Ligny, Bruno Hurault, Fischbach, Michel, Gupta, Ritu, Hauhart, Richard, Meunier, Vincent, Loirat, Chantal, Dragon-Durey, Marie-Agnès, Fridman, Wolf H., Janssen, Bert J.C., Goodship, Timothy H.J., and Atkinson, John P.

Published
2008
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30. Pregnancy-Associated Hemolytic Uremic Syndrome Revisited in the Era of Complement Gene Mutations

Author

Fakhouri, Fadi, primary, Roumenina, Lubka, additional, Provot, François, additional, Sallée, Marion, additional, Caillard, Sophie, additional, Couzi, Lionel, additional, Essig, Marie, additional, Ribes, David, additional, Dragon-Durey, Marie-Agnès, additional, Bridoux, Frank, additional, Rondeau, Eric, additional, and Frémeaux-Bacchi, Veronique, additional

Published
2010
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34. Features of myositis and myasthenia gravis in patients treated with immune checkpoint inhibitors: a multicentric, retrospective cohort study.

Author

Plomp L, Chassepot H, Psimaras D, Maisonobe T, Mensi E, Leonard-Louis S, Plu I, Rozes A, Tubach F, Touat M, Anquetil C, Wesner N, Champtiaux N, Rigolet A, Demeret S, Weiss N, Alyanakian MA, Le Panse R, Truffault F, Dragon-Durey MA, Chatenoud L, Abbar B, Bretagne MC, Procureur A, Similowski T, Morelot-Panzini C, Dres M, Ederhy S, Benveniste O, Salem JE, and Allenbach Y

Abstract

Background: Immune checkpoint inhibitors (ICIs) may induce overlapping myositis/myasthenia gravis (MG) features, sparking current debate about pathophysiology and management of this emerging disease entity. We aimed to clarify whether ICI-induced (ir-) myositis and ir-MG represent distinct diseases or exist concurrently., Methods: We performed a retrospective multicenter cohort study. Using the Paris University Hospitals database (n = 2,910,417), we screened all patients with International Classification of Diseases codes or free text related to myositis/MG signs and ICI (n = 620). 'Ir-MG signs' were defined by fatigability, repetitive nerve stimulation (RNS) decrement, and/or acetylcholine receptor antibodies (AChR Abs)., Findings: Ir-MG signs were never observed in the absence of ir-myositis (pathological diagnosis (n = 12/14) or CK levels >8000 U/L (n = 2/14)). Among ir-myositis patients, fatigability (2%; n = 1/62) and RNS decrement (2%; n = 1/41) were demonstrated only in one patient with pre-existing MG. AChR Abs testing yielded positive results in 26% of ir-myositis patients (n = 14/53). We revealed that test results were already positive prior to ICI therapy (n = 8/9). Clinically, ir-myositis frequently presented with "MG-like" oculomotor disease (50%; n = 31/62), bulbar dysfunction affecting speech (29%; n = 18/62) and swallowing (42%; n = 26/62), and respiratory disorders (53%; n = 33/62). Extraocular and diaphragm muscles necropsies disclosed intense muscle inflammation (100%; n = 5/5)., Interpretation: In our extensive database, we found no evidence of isolated ir-MG, nor of clear neuromuscular junction dysfunction in ir-myositis. These findings suggest that patients with ir-MG suspicion frequently have ir-myositis and ir-MG might be rare. "MG-like" symptoms may stem from ir-myositis-specific predilection for oculo-bulbo-respiratory musculature. Indeed, we revealed florid inflammatory infiltration of the oculomotor and respiratory muscles. Additional studies are needed to confirm these results and to elucidate the role of pre-existing AChR Abs in ir-myositis., Funding: None., Competing Interests: None of the authors received financial support for the submitted work. CA reports one patent planned in the field of management of immune checkpoint inhibitors toxicities. BA reports a research grant from MSD Avenir, consulting fees from Novartis, Astellas, and Sanofi, personal honorarium from Sanofi, AstraZeneca, BMS, MSD and Astellas, and support for attending meetings and/or travel from Janssen, MSD, Pfizer, IPSEN Pharma and Takeda. MT reports a grant from Sanofi, consulting fees from Servier, Novocure and NH TherAguiX, personal honorarium from Servier, Novocure and ONO, and support for attending meetings and/or travel from Servier. MT participated on a Data Safety Monitoring or Advisory Board for Servier. MCB reports personal honorarium, and support for attending meetings and/or travel from Novartis. SE reports consulting fees from Bayer, Amgen and Ipsen, and personal honorarium from AstraZeneca, BMS, Philips, General Electric, and Eisai. FT reports non-personal consulting fees from MSD, Novartis, and GSK. JES reports personal consulting fees from AstraZeneca, BeiGene, BMS and Novartis, several patents planned, issued or pending in the field of management of immune checkpoint inhibitors toxicities. YA received research funding from Sanofi and Association Recherche contre le Cancer, consulting fees from BMS, personal honorarium from RE-IMAGINE Health Agency and CSL Behring SA, and support for attending meetings and/or travel from CSL Behring SA and Boehringer Ingelheim France. YA had several patents planned, issued or pending in the field of management of immune checkpoint inhibitors toxicities., (© 2025 The Authors.)

Published
2025
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35. Immune Signature Linked to COVID-19 Severity: A SARS-Score for Personalized Medicine.

Author

Russick J, Foy PE, Josseaume N, Meylan M, Hamouda NB, Kirilovsky A, Sissy CE, Tartour E, Smadja DM, Karras A, Hulot JS, Livrozet M, Fayol A, Arlet JB, Diehl JL, Dragon-Durey MA, Pagès F, and Cremer I

Subjects
Adaptive Immunity genetics, Adult, Aged, Antiviral Agents therapeutic use, Biomarkers, COVID-19 therapy, Cohort Studies, Female, Hospitalization, Humans, Inflammation genetics, Male, Middle Aged, Precision Medicine, Prospective Studies, Severity of Illness Index, Transcriptome, COVID-19 immunology, SARS-CoV-2 physiology
Abstract

SARS-CoV-2 infection leads to a highly variable clinical evolution, ranging from asymptomatic to severe disease with acute respiratory distress syndrome, requiring intensive care units (ICU) admission. The optimal management of hospitalized patients has become a worldwide concern and identification of immune biomarkers predictive of the clinical outcome for hospitalized patients remains a major challenge. Immunophenotyping and transcriptomic analysis of hospitalized COVID-19 patients at admission allow identifying the two categories of patients. Inflammation, high neutrophil activation, dysfunctional monocytic response and a strongly impaired adaptive immune response was observed in patients who will experience the more severe form of the disease. This observation was validated in an independent cohort of patients. Using in silico analysis on drug signature database, we identify differential therapeutics that specifically correspond to each group of patients. From this signature, we propose a score-the SARS-Score-composed of easily quantifiable biomarkers, to classify hospitalized patients upon arrival to adapt treatment according to their immune profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Russick, Foy, Josseaume, Meylan, Hamouda, Kirilovsky, Sissy, Tartour, Smadja, Karras, Hulot, Livrozet, Fayol, Arlet, Diehl, Dragon-Durey, Pagès and Cremer.)

Published
2021
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36. Serum Gp96 is a chaperone of complement-C3 during graft-versus-host disease.

Author

Seignez A, Joly AL, Chaumonnot K, Hazoumé A, Sanka M, Marcion G, Boudesco C, Hammann A, Seigneuric R, Jégo G, Ducoroy P, Delarue P, Senet P, Castilla-Llorente C, Solary E, Durey MA, Rubio MT, Hermine O, Kohli E, and Garrido C

Subjects
Adolescent, Adult, Animals, Complement Activation, Hematopoietic Stem Cell Transplantation, Humans, Mice, Middle Aged, Young Adult, Complement C3 metabolism, Graft vs Host Disease blood, Membrane Glycoproteins blood, Molecular Chaperones blood
Abstract

Better identification of severe acute graft-versus-host disease (GvHD) may improve the outcome of this life-threatening complication of allogeneic hematopoietic stem cell transplantation. GvHD induces tissue damage and the release of damage-associated molecular pattern (DAMP) molecules. Here, we analyzed GvHD patients ( n = 39) to show that serum heat shock protein glycoprotein 96 (Gp96) could be such a DAMP molecule. We demonstrate that serum Gp96 increases in gastrointestinal GvHD patients and its level correlates with disease severity. An increase in Gp96 serum level was also observed in a mouse model of acute GvHD. This model was used to identify complement C3 as a main partner of Gp96 in the serum. Our biolayer interferometry, yeast two-hybrid and in silico modeling data allowed us to determine that Gp96 binds to a complement C3 fragment encompassing amino acids 749-954, a functional complement C3 hot spot important for binding of different regulators. Accordingly, in vitro experiments with purified proteins demonstrate that Gp96 downregulates several complement C3 functions. Finally, experimental induction of GvHD in complement C3-deficient mice confirms the link between Gp96 and complement C3 in the serum and with the severity of the disease., Competing Interests: Conflict of interest: The authors have declared that no conflict of interest exists.

Published
2017
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37. Y402H complement factor H polymorphism associated with exudative age-related macular degeneration in the French population.

Author

Souied EH, Leveziel N, Richard F, Dragon-Durey MA, Coscas G, Soubrane G, Benlian P, and Fremeaux-Bacchi V

Subjects
Aged, Complement Factor H genetics, DNA Mutational Analysis, Exons genetics, Exudates and Transudates, Female, France epidemiology, Gene Frequency, Humans, Macular Degeneration ethnology, Male, Mutation, Odds Ratio, Polymerase Chain Reaction, Sequence Analysis, DNA, White People, Macular Degeneration genetics, Polymorphism, Single Nucleotide
Abstract

Purpose: Identification of genetic factors for age-related macular degeneration (AMD) is of crucial importance in this common cause of blindness. A positive association between Y402H polymorphism of the complement factor H (CFH) gene and AMD has been recently reported in North American populations but not yet in European populations. The exudative form of AMD is rapidly progressive and usually associated with a severe prognosis. Our purpose was to investigate this association in a French population specifically affected with exudative AMD, in a case-control study., Methods: Two series of unrelated exudative AMD patients, sporadic cases (n=60, mean age 74.9+/-5.7) and familial cases (n=81, mean age 74.0+/-9.4) were compared with healthy controls (n=91, mean age 74.6+/-6.3). The coding region of exon 9 of CFH was examined for the Y402H polymorphism by PCR-direct sequencing., Results: The 1,279-C allele frequencies were significantly higher in exudative AMD patients than controls (0.564 compared to 0.302; p<0.0001). Genotypic distribution of the Y402H polymorphism was significantly different between sporadic cases compared to controls (chi2=14.48 with 2 df, p<0.0007) and between familial cases compared to controls (chi2=23.78 with 2 df, p<0.0001). The odds ratio (OR) for exudative AMD was 3.00 CI95% (1.60-5.62) for heterozygotes (CT) and 6.93 CI95% (3.11-15.46) for homozygotes (CC)., Conclusions: These results suggest the contribution of the Y402H polymorphism of the CFH gene to exudative AMD susceptibility also in the French population. This relationship with the CFH may lead to early detection and new strategies for prevention and treatment of AMD.

Published
2005

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