13 results on '"Balsera-Manzanero, María"'
Search Results
2. Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
- Author
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Balsera-Manzanero, María, Soengas, Raquel G., Carretero-Ledesma, Marta, Ratia, Carlos, Iglesias, M. José, Pachón, Jerónimo, López-Ortiz, Fernando, Cordero, Elisa, Soto, Sara M., and Sánchez-Céspedes, Javier
- Published
- 2024
- Full Text
- View/download PDF
3. Antiviral activity of immunosuppressors alone and in combination against human adenovirus and cytomegalovirus
- Author
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Carretero-Ledesma, Marta, primary, Aguilar-Guisado, Manuela, additional, Berastegui-Cabrera, Judith, additional, Balsera-Manzanero, María, additional, Pachón, Jerónimo, additional, Cordero, Elisa, additional, and Sánchez-Céspedes, Javier, additional
- Published
- 2024
- Full Text
- View/download PDF
4. Mecanismos inmunitarios y virológicos implicados en el desarrollo y protección de la neumonía gripal en adultos
- Author
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Cordero Matia, María Elisa, Sánchez Céspedes, Javier, Universidad de Sevilla. Departamento de Medicina, Balsera-Manzanero, María, Cordero Matia, María Elisa, Sánchez Céspedes, Javier, Universidad de Sevilla. Departamento de Medicina, and Balsera-Manzanero, María
- Abstract
La gripe es una enfermedad infecciosa que genera importantes epidemias anuales, con un impacto económico y social significativo a nivel global. Entre sus complicaciones más graves se encuentra la neumonía. Tradicionalmente, se ha subestimado el rol de los virus en la neumonía comunitaria, pero el uso extendido de técnicas de diagnóstico molecular, como la PCR, ha evidenciado un incremento en la identificación de virus respiratorios como agentes causales de esta enfermedad. Por otro lado, la respuesta inmune es esencial para controlar la infección por el virus influenza, no obstante, son escasos los estudios que exploran cómo la vacunación contra la gripe afecta tanto a la inmunidad innata como a la adaptativa en pacientes ingresados con gripe y cuál es su relación con la gravedad y el desenlace clínico. El objetivo principal de este trabajo es identificar cómo varía la respuesta inmune frente a la gripe según la gravedad y el desenlace clínico de pacientes hospitalizados por gripe y el impacto de la vacunación en esta respuesta y compararla con la respuesta inmunitaria inducida por la administración de la vacuna antigripal en voluntarios sanos. Además, en el contexto de co-circulación de influenza y SARS-CoV-2, se propuso comparar la respuesta vacunal frente a la vacunación conjunta frente a gripe y COVID-19 con la vacunación antigripal única. Los resultados del presente trabajo ponen de manifiesto diferencias en la respuesta inmune frente a la gripe según el desenlace clínico y el estado de vacunación. La concentración sérica de IL-10 al ingreso se relacionó con la infección natural por el virus de la gripe, así como, con el desenlace desfavorable de los pacientes hospitalizados por gripe. Sin embargo, tener niveles detectables de IL-1? precozmente se relacionó con la vacunación. No obstante, la seroprotección precoz fue mayor en los voluntarios sanos vacunados que en los pacientes ingresados por gripe, independientemente a la edad y la presencia de comorbilidades.
- Published
- 2024
5. Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
- Author
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Universidad de Sevilla. Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBIS), Balsera-Manzanero, María, Ghirga, Francesca, Ruiz-Molina, Ana, Mori, Mattia, Pachón Díaz, Jerónimo, Botta, Bruno, Cordero Matia, María Elisa, Quaglio, Deborah, Sanchez Cespedes, Javier, Universidad de Sevilla. Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBIS), Balsera-Manzanero, María, Ghirga, Francesca, Ruiz-Molina, Ana, Mori, Mattia, Pachón Díaz, Jerónimo, Botta, Bruno, Cordero Matia, María Elisa, Quaglio, Deborah, and Sanchez Cespedes, Javier
- Abstract
Regardless of the clinical impact of human adenovirus (HAdV) infections in the healthy population and its high morbidity in immunosuppressed patients, a specific treatment is still not yet available. In this study, we screened the CM1407 COST Action’s chemical library, comprising 1,233 natural products to identify compounds that restrict HAdV infection. Among them, we identified rotenolone, a compound that significantly inhibited HAdV infection. Next, we selected four isoflavonoid-type compounds (e.g., rotenone, deguelin, millettone, and tephrosin), namely rotenoids, structurally related to rotenolone in order to evaluate and characterized in vitro their antiviral activities against HAdV and human cytomegalovirus (HCMV). Their IC50 values for HAdV ranged from 0.0039 µM for rotenone to 0.07 µM for tephrosin, with selective indices ranging from 164.1 for rotenone to 2,429.3 for deguelin. In addition, the inhibition of HCMV replication ranged from 50% to 92.1% at twice the IC50 concentrations obtained in the plaque assay for each compound against HAdV. Our results indicated that the mechanisms of action of rotenolone, deguelin, and tephrosin involve the late stages of the HAdV replication cycle. However, the antiviral mechanism of action of rotenone appears to involve the alteration of the microtubular polymerization, which prevents HAdV particles from reaching the nuclear membrane of the cell. These isoflavonoid-type compounds exert high antiviral activity against HAdV at nanomolar concentrations, and can be considered strong hit candidates for the development of a new class of broad-spectrum antiviral drugs.
- Published
- 2024
6. Heteroleptic (S^C)-cyclometallated gold(III) complexes as novel antiviral agents
- Author
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Universidad de Sevilla. Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBIS), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Balsera-Manzanero, María, Soengas, Raquel G., Carretero-Ledesma, Marta, Ratia, Carlos, Iglesias, M. José, Pachón Díaz, Jerónimo, López-Ortiz, Fernando, Cordero Matia, María Elisa, Soto, Sara M., Sanchez Cespedes, Javier, Universidad de Sevilla. Departamento de Medicina, Instituto de Biomedicina de Sevilla (IBIS), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación, Balsera-Manzanero, María, Soengas, Raquel G., Carretero-Ledesma, Marta, Ratia, Carlos, Iglesias, M. José, Pachón Díaz, Jerónimo, López-Ortiz, Fernando, Cordero Matia, María Elisa, Soto, Sara M., and Sanchez Cespedes, Javier
- Abstract
Despite the increasingly widespread clinical impact of adenovirus (HAdV) infections in healthy individuals and the associated high morbidity in immunosuppressed patients, particularly among the paediatric population, a specific treatment for this virus has yet to be developed. In this study, we report the anti-HAdV activity of sub-micromolar concentrations of four heteroleptic (C^S)- cycloaurated complexes bearing a single thiophosphinamide [Au(dpta)Cl2, Au(dpta)(mrdtc), and Au(dpta)(dedtc)] or thiophosphonamide [Au(bpta)(dedtc)] chelating ligand and a dithiocarbamate moiety. In addition to their low cytotoxicity, the findings of mechanistic assays revealed that these molecules have antiviral activity by targeting stages of the viral replication cycle subsequent to DNA replication. Additionally, all four compounds showed a significant inhibition of human cytomegalovirus (HCMV) DNA replication, thereby providing evidence for potential broad-spectrum antiviral activity.
- Published
- 2024
7. Dysregulation in host sphingolipid metabolism caused by West Nile virus infection as a potential disease progression biomarker and new therapeutic target
- Author
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European Commission, Mingo-Casas, Patricia [0000-0003-1207-240X], Sanchez-Céspedes, Javier [0000-0003-2707-1979], Blázquez, Ana B. [0000-0002-0847-0977], Casas, Josefina [0000-0002-7926-5209], Balsera-Manzanero, María [0000-0001-5667-925X], Herrero, Laura [0000-0003-4244-4673], Pachón, Jerónimo [0000-0002-8166-5308], Aguilar-Guisado, Manuela [0000-0001-5639-9434], Mingo-Casas, Patricia, Sanchez-Céspedes, Javier, Blázquez, Ana B., Casas, Josefina, Balsera-Manzanero, María, Herrero, Laura, Vázquez, Ana, Pachón, Jerónimo, Aguilar-Guisado, Manuela, European Commission, Mingo-Casas, Patricia [0000-0003-1207-240X], Sanchez-Céspedes, Javier [0000-0003-2707-1979], Blázquez, Ana B. [0000-0002-0847-0977], Casas, Josefina [0000-0002-7926-5209], Balsera-Manzanero, María [0000-0001-5667-925X], Herrero, Laura [0000-0003-4244-4673], Pachón, Jerónimo [0000-0002-8166-5308], Aguilar-Guisado, Manuela [0000-0001-5639-9434], Mingo-Casas, Patricia, Sanchez-Céspedes, Javier, Blázquez, Ana B., Casas, Josefina, Balsera-Manzanero, María, Herrero, Laura, Vázquez, Ana, Pachón, Jerónimo, and Aguilar-Guisado, Manuela
- Abstract
West Nile virus (WNV) is a neurotropic flavivirus transmitted by the bites of infected Culex sp mosquitoes and it is widely distributed across Europe. Severe forms of West Nile disease (WND) can cause meningitis, encephalitis or even death. In 2020, WNV caused an outbreak in southwest Spain that ended up with 70 human infections and 7 deaths. There are no vaccines or specific drugs to prevent and treat the symptoms of WND in humans, so the search for novel targets for therapeutic interventions is mandatory. Lipid metabolism is gaining interest as a potential target to combat flavivirus using a host-targeted approach.
- Published
- 2023
8. Lipid signatures of West Nile virus infection unveil alterations of sphingolipid metabolism providing novel biomarkers
- Author
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Mingo-Casas, Patricia, primary, Sanchez-Céspedes, Javier, additional, Blázquez, Ana-Belén, additional, Casas, Josefina, additional, Balsera-Manzanero, María, additional, Herrero, Laura, additional, Vázquez, Ana, additional, Pachón, Jerónimo, additional, Aguilar-Guisado, Manuela, additional, Cisneros, José Miguel, additional, Saiz, Juan-Carlos, additional, and Martín-Acebes, Miguel A., additional
- Published
- 2023
- Full Text
- View/download PDF
9. Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone.
- Author
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Balsera-Manzanero, María, Ghirga, Francesca, Ruiz-Molina, Ana, Mori, Mattia, Pachón, Jerónimo, Botta, Bruno, Cordero, Elisa, Quaglio, Deborah, and Sánchez-Céspedes, Javier
- Subjects
ROTENONE ,ADENOVIRUSES ,HUMAN cytomegalovirus ,CHEMICAL libraries ,NUCLEAR membranes ,ANTIVIRAL agents ,CELL nuclei - Abstract
Regardless of the clinical impact of human adenovirus (HAdV) infections in the healthy population and its high morbidity in immunosuppressed patients, a specific treatment is still not yet available. In this study, we screened the CM1407 COST Action's chemical library, comprising 1,233 natural products to identify compounds that restrict HAdV infection. Among them, we identified rotenolone, a compound that significantly inhibited HAdV infection. Next, we selected four isoflavonoid-type compounds (e.g., rotenone, deguelin, millettone, and tephrosin), namely rotenoids, structurally related to rotenolone in order to evaluate and characterized in vitro their antiviral activities against HAdV and human cytomegalovirus (HCMV). Their IC
50 values for HAdV ranged from 0.0039 µM for rotenone to 0.07 µM for tephrosin, with selective indices ranging from 164.1 for rotenone to 2,429.3 for deguelin. In addition, the inhibition of HCMV replication ranged from 50% to 92.1% at twice the IC50 concentrations obtained in the plaque assay for each compound against HAdV. Our results indicated that the mechanisms of action of rotenolone, deguelin, and tephrosin involve the late stages of the HAdV replication cycle. However, the antiviral mechanism of action of rotenone appears to involve the alteration of the microtubular polymerization, which prevents HAdV particles from reaching the nuclear membrane of the cell. These isoflavonoid-type compounds exert high antiviral activity against HAdV at nanomolar concentrations, and can be considered strong hit candidates for the development of a new class of broad-spectrum antiviral drugs. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
10. Lipid signatures of West Nile virus infection unveil alterations of sphingolipid metabolism providing novel biomarkers
- Author
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Ministerio de Ciencia e Innovación (España), 0000-0003-1207-240X, 0000-0003-2707-1979, 0000-0002-0847-0977, 0000-0002-7926-5209, 0000-0001-5667-925X, 0000-0002-9872-3316, 0000-0002-8166-5308, 0000-0001-5639-9434, 0000-0001-5001-672X, 0000-0001-8269-5544, 0000-0001-6015-3613, Mingo-Casas, Patricia, Sánchez-Céspedes, Javier, Blázquez, Ana-Belén, Casas, Josefina, Balsera-Manzanero, María, Herrero, Laura, Vázquez, Ana, Pachón, Jerónimo, Aguilar-Guisado, Manuela, Cisneros, José Miguel, Saiz Calahorra, Juan Carlos, Martín-Acebes, M. A., Ministerio de Ciencia e Innovación (España), 0000-0003-1207-240X, 0000-0003-2707-1979, 0000-0002-0847-0977, 0000-0002-7926-5209, 0000-0001-5667-925X, 0000-0002-9872-3316, 0000-0002-8166-5308, 0000-0001-5639-9434, 0000-0001-5001-672X, 0000-0001-8269-5544, 0000-0001-6015-3613, Mingo-Casas, Patricia, Sánchez-Céspedes, Javier, Blázquez, Ana-Belén, Casas, Josefina, Balsera-Manzanero, María, Herrero, Laura, Vázquez, Ana, Pachón, Jerónimo, Aguilar-Guisado, Manuela, Cisneros, José Miguel, Saiz Calahorra, Juan Carlos, and Martín-Acebes, M. A.
- Abstract
West Nile virus (WNV) is a neurotropic flavivirus transmitted by the bites of infected mosquitoes. Severe forms of West Nile disease (WND) can curse with meningitis, encephalitis or acute flaccid paralysis. A better understanding of the physiopathology associated with disease progression is mandatory to find biomarkers and effective therapies. In this scenario, blood derivatives (plasma and serum) constitute the more commonly used biofluids due to its ease of collection and high value for diagnostic purposes. Therefore, the potential impact of this virus in the circulating lipidome was addressed combining the analysis of samples from experimentally infected mice and naturally WND patients. Our results unveil dynamic alterations in the lipidome that define specific metabolic fingerprints of different infection stages. Concomitant with neuroinvasion in mice, the lipid landscape was dominated by a metabolic reprograming that resulted in significant elevations of circulating sphingolipids (ceramides, dihydroceramides, and dihydrosphingomyelins), phosphatidylethanolamines and triacylglycerols. Remarkably, patients suffering from WND also displayed an elevation of ceramides, dihydroceramides, lactosylceramides, and monoacylglycerols in their sera. The dysregulation of sphingolipid metabolism by WNV may provide new therapeutic opportunities and supports the potential of certain lipids as novel peripheral biomarkers of WND progression.
- Published
- 2023
11. Inhibition of adenovirus transport from the endosome to the cell nucleus by rotenone
- Author
-
European Commission, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Red Española de Investigación en Patología Infecciosa, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Servicio Andaluz de Salud, Junta de Andalucía, Balsera-Manzanero, María, Ghirga, Francesca, Ruiz-Molina, Ana, Mori, Mattia, Pachón, Jerónimo, Botta, Bruno, Cordero-Matía, Elisa, Quaglio, Deborah, Sánchez-Céspedes, Javier, European Commission, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Red Española de Investigación en Patología Infecciosa, Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), Servicio Andaluz de Salud, Junta de Andalucía, Balsera-Manzanero, María, Ghirga, Francesca, Ruiz-Molina, Ana, Mori, Mattia, Pachón, Jerónimo, Botta, Bruno, Cordero-Matía, Elisa, Quaglio, Deborah, and Sánchez-Céspedes, Javier
- Abstract
Regardless of the clinical impact of human adenovirus (HAdV) infections in the healthy population and its high morbidity in immunosuppressed patients, a specific treatment is still not yet available. In this study, we screened the CM1407 COST Action’s chemical library, comprising 1,233 natural products to identify compounds that restrict HAdV infection. Among them, we identified rotenolone, a compound that significantly inhibited HAdV infection. Next, we selected four isoflavonoid-type compounds (e.g., rotenone, deguelin, millettone, and tephrosin), namely rotenoids, structurally related to rotenolone in order to evaluate and characterized in vitro their antiviral activities against HAdV and human cytomegalovirus (HCMV). Their IC50 values for HAdV ranged from 0.0039 µM for rotenone to 0.07 µM for tephrosin, with selective indices ranging from 164.1 for rotenone to 2,429.3 for deguelin. In addition, the inhibition of HCMV replication ranged from 50% to 92.1% at twice the IC50 concentrations obtained in the plaque assay for each compound against HAdV. Our results indicated that the mechanisms of action of rotenolone, deguelin, and tephrosin involve the late stages of the HAdV replication cycle. However, the antiviral mechanism of action of rotenone appears to involve the alteration of the microtubular polymerization, which prevents HAdV particles from reaching the nuclear membrane of the cell. These isoflavonoid-type compounds exert high antiviral activity against HAdV at nanomolar concentrations, and can be considered strong hit candidates for the development of a new class of broad-spectrum antiviral drugs.
- Published
- 2023
12. Autoantibodies against type I IFNs in patients with critical influenza pneumonia
- Author
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Zhang, Qian, Pizzorno, Andrés, Miorin, Lisa, Bastard, Paul, Gervais, Adrian, Le Voyer, Tom, Bizien, Lucy, Manry, Jeremy, Rosain, Jérémie, Philippot, Quentin, Goavec, Kelian, Wroblewski, Isabelle, Husebye, Eystein, Fellay, Jacques, Pothier, Pierre, Morand, Patrice, Navarrete, Nicolás, Franco, José Luis, Uddin, Mohammed J., Carratalà, Jordi, Merino Díaz, Laura, Palomo, Virginia, Seppänen, Mikko R.J., Särekannu, Karita, Aiuti, Alessandro, Retamar Gentil, Pilar, Debette, Stéphanie, Belot, Alexandre, Abel, Laurent, Soler Palacín, Pere, Abad Arranz, Maria, Aguilar Guisado, Manuela, Meyts, Isabelle, Casanova, Jean-Laurent, Gonzalez Granado, Luis L., Butte, Manish J., Itan, Yuval, Escoresca Ortega, Ana, Morio, Tomohiro, Padey, Blandine, Niubó, Jordi, Gallardo Ríos, Rafaela, Lau, Yu-lung, Triantafyllia, Vasiliki, Briones, Marisa, Saker, Kahina, Richard, Pascale, Drolet, Beth A., Espinosa Padilla, Sara, Wauters, Joost, Peigue Lafeuille, Helene, Valiente, Adoración, El Baghdadi, Jamila, Tiberghien, Pierre, Balsera-manzanero, María, Zins, Marie, Hammarström, Lennart, Andreakos, Evangelos, Notarangelo, Luigi D., Prando, Carolina, Condino-neto, Antonio, Dominguez Pinilla, Nerea, Aydillo, Teresa, Okamoto, Keisuke, Soumaré, Aïcha, Karamitros, Timokratis, Medina, Rafael A., Kisand, Kai, Ramírez Duque, Nieves, Feys, Simon, Romero Oraa, Laura, Kuo, Chen-yen, Lei, Wei-te, Quintana Murci, Lluis, Milner, Joshua D., Ku, Cheng-lung, Van De Beek, Diederik, Hsieh, Elena W.Y., Tal, Galit, Fournet, Thomas, Cerba Healthcare Group, Patural, Hugues, Novelli, Giuseppe, Lyon Antigrippe Working Group, Arias, Andrés A., Rovina, Nikoletta, Rodríguez-gallego, Carlos, Puel, Anne, Jouanguy, Emmanuelle, Vinh, Donald C., Henny, Joseph, Mogensen, Trine H., Cobat, Aurélie, Casari, Giorgio, Ramaswamy, Sathishkumar, Abelenda Alonso, Gabriela, Morel, Pascal, Trouillet Assant, Sophie, Tzourio, Christophe, Gallian, Pierre, Reipi Inf Working Group, García Sastre, Adolfo, Constantinescu, Stefan N., Hamzeh Cognasse, Hind, Haerynck, Filomeen, Flores, Carlos, Bousfiha, Ahmed A., García Salum, Tamara, Shahrooei, Mohammed, Slaby, Ondrej, Fragkou, Paraskevi C., Argaud, Laurent, Shcherbina, Anna, Al-muhsen, Saleh, Biggs, Catherine M., Bogunovic, Dusan, Planas, Anna M., Heath, James R., Von Bernuth, Horst, Dufouil, Carole, Bolze, Alexandre, Boeuf, Benoit, Rodríguez Gallego, Carlos, Christodoulou, John, Bondarenko, Anastasiia, Martin, Fernando, Koltsida, Ourania, Sediva, Anna, Ruiz Hernandez, José Juan, Bonneaudeau, Brigitte, Cannet, Dorothée, Etablissement Français Du Sang Study Group, Froidure, Antoine, Laurent, Emilie, Galani, Ioanna Evdokia, Gregersen, Peter K., Lemonnier, Sylvie, Spaan, András N., Darmon, Michael, Grimbacher, Bodo, Del Mar Muñoz Garcia, Maria, Zawadzki, Pawel, Henrickson, Sarah E., O'farrelly, Cliona, Rosa Calatrava, Manuel, Lachaize, Morgane, Okada, Satoshi, Vanker, Martti, Bryceson, Yenan, Ling, Yun, Cooper, Megan A., Lucas, Carrie L., Maniatis, Tom, Romero Vázquez, Gloria María, Mansouri, Davood, Castagnoli, Riccardo, Maródi, László, Mironska, Kristina, Rapti, Vasiliki, Baris Feldman, Hagit, Pozzetto, Bruno, Renia, Laurent, Tancevski, Ivan, Imai, Kohsuke, Ozcelik, Tayfun, Pan-hammarström, Qiang, Al-mulla, Fahd, Pape, Jean W., Etzioni, Amos, Souweine, Bertrand, Perez De Diego, Rebeca, Sánchez Cordero, Maria Jose, Solé Violán, Jordi, Perlin, David S., Queromes, Gregory, Anderson, Mark S., Resnick, Igor, Pesole, Graziano, Su, Helen C., Vanderbeke, Lore, Hagin, David, Jeanne, Michel, Desai, Murkesh, Ferres, Marcela, Sánchez Céspedes, Javier, Perroquin, Magali, Ng, Lisa F.P., Abou Tayoun, Ahmad, Le Corre, Nicole, Snow, Andrew L., Temel, Şehime Gülsün, Tsiodras, Sotirios, Coeuret Pellicer, Mireille, Javouhey, Etienne, Turvey, Stuart E., Covid Human Genetic Effort, Rombauts, Alexander, Zatz, Mayana, Uddin, K.m. Furkan, Fievet, Nathalie, Jarvis, Erich D., Rodríguez De Castro, Felipe, Ferreres, José, Flaig, Amandine, Pujol, Aurora, Cognasse, Fabrice, Sancho Shimizu, Vanessa, Nadif, Rachel, Hanna, Suhair, Constances Cohort, Goldberg, Marcel, Brodin, Petter, Le Got, Stéphane, Ozguler, Anna, Quenot, Jean Pierre, Novelli, Antonio, Cordero, Elisa, Colomb, Benoit, Cupic, Anastasija, Mehlal Sedkaoui, Souad, Sallette, Jérôme, Hernu, Romain, Bustamante, Carlos D., Lina, Bruno, Halwani, Rabih, Casalegno, Jean Sebastien, Schwebel, Carole, Salamanca Rivera, Celia, 3C-Dijon Study, Tangye, Stuart G., Dalgard, Clifton L., Howard Hughes Medical Institute, Rockefeller University, St. Giles Foundation, National Institutes of Health (US), National Center for Advancing Translational Sciences (US), Fisher Center for Alzheimer's Research Foundation, Meyer Foundation, JPB Foundation, Agence Nationale de la Recherche (France), European Commission, Square Foundation, Ministre de l'Enseignement Supérieur, de la Recherche et de l'Innovation (France), Institut National de la Santé et de la Recherche Médicale (France), Université Paris Cité, Center for Research for Influenza Pathogenesis (US), National Institute of Allergy and Infectious Diseases (US), Center of Excellence for Influenza Research and Response (US) CEIRR, Agencia Nacional de Investigación y Desarrollo (Chile), Centre National de la Recherche Scientifique (France), Ministère des Solidarités et de la Santé (France), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación (España), Fundación Mapfre, Sociedad Española de Neumología y Cirugía Torácica, Cabildo de Tenerife, Hellenic Foundation for Research and Innovation, Fondation pour la Recherche Médicale, Fondation Bettencourt Schueller, Ministerio de Ciencia, Innovación y Universidades (España), Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (España), Junta de Andalucía, Research Foundation - Flanders, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), 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), Etablissement Français du Sang [La Plaine Saint-Denis] (EFS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire de Biotechnologie et Microbiologie Appliquée (LBMA), Université Bordeaux Segalen - Bordeaux 2-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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), Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), 01057100, HORIZON-HLTH-2021-DISEASE-04, MESRI-COVID-19, ANR-10-LABX-62-IBEID, P18-RT-3320, CGIEU0000219140, RTC-2017-6471-1, REIPI RD16/0016/0009, National Institutes of Health, NIH: R01AI088364, R01AI163029, Howard Hughes Medical Institute, HHMI, National Institute of Allergy and Infectious Diseases, NIAID: 75N93021C00014, U19AI135972, U19AI142733, U19AI168631, Jeffrey Modell Foundation, JMF, Glenn Foundation for Medical Research, GFMR: ANRS-COV05, EA20170638020, EQU201903007798, Pfizer, Albert Ellis Institute, AEI, National Center for Advancing Translational Sciences, NCATS: UL1 TR001866, JPB Foundation, JPBF, Horizon 2020 Framework Programme, H2020: 824110, Fondation du Souffle, FdS, College of Natural Resources and Sciences, Humboldt State University, CNRS, Ministerio de Ciencia, Innovación y Universidades, MCIU, Instituto Tecnológico y de Energías Renovables, ITER, SCOR Corporate Foundation for Science, Agence Nationale de la Recherche, ANR: ANR-10-IAHU-01, Institut National de la Santé et de la Recherche Médicale, Inserm, Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT: 1161971, 1212023, Association Nationale de la Recherche et de la Technologie, ANRT, Fonds Wetenschappelijk Onderzoek, FWO: G0B5120N, G0C8517N, G0E8420N, KU Leuven: C16/18/007, Instituto de Salud Carlos III, ISCIII: COV20_01333, COV20_01334, PI12/01565, European Regional Development Fund, ERDF: CB21/13/00006, University of the East, UE, Hellenic Foundation for Research and Innovation, ΕΛ.ΙΔ.Ε.Κ, Université de Paris, SINOVAC outside the submitted work. P. Retamar-Gentil reported personal fees from Merck outside the submitted work. I. Meyts reported grants from CSL-Behring outside the submitted work. E. Andreakos reported grants from Janssen Pharmaceuticals during the conduct of the study. J. Wauters reported grants and personal fees from Pfizer and Gilead outside the submitted work. L. Vanderbeke reported grants from Research Foundation Flanders and non-financial support from Pfizer outside the submitted work. S. Feys reported grants from Pfizer outside the submitted work. J. Casalegno reported 'other' from Pfizer and grants from Sanofi outside the submitted work. M. Rosa-Calatrava reported a patent to WO2016/146836 licensed (Signia Therapeutics), a patent to WO2017/174593 licensed (Signia Therapeutics), and a patent to WO2019/224489 licensed (Signia Therapeutics), and is the co-founder of Signia Therapeutics SAS. S. Trouillet-Assant reported non-financial support from BioMérieux outside the submitted work. A. Garcia-Sastre reported 'other' from Vivaldi Biosciences, Pagoda, Contrafect, Vaxalto, Accurius, Curelab oncology, and Curelab veterinary, personal fees from Avimex, 7Hills, Esperovax, Pfizer, Farmak, Applied Biological Laboratories, Paratus, Pharmamar, Pfizer, and Synairgen, grants from Pfizer, Pharmamar, Blade Therapeutics, Avimex, Accurius, Dyna-vax, Kenall Manufacturing, ImmunityBio, Nanocomposix, Merck, Model Medicines, Atea Pharma, Shenwa Biosciences, Johnson & Johnson, 7 Hills, Hexamer, N-fold LLC, and Applied Biological Laboratories outside the submitted work, in addition, A. Garcia-Sastre had a patent for influenza virus vaccines and uses thereof issued, and invited speaker in meeting events organized by Seqirus, Janssen, Abbott, and Astrazeneca. J. Casanova reported a patent to PCT/US2021/ 042741 pending. No other disclosures were reported., We thank Dr. Cato Jacobs for her contribution to the sampling of UZLeuven patients in Belgium. The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Sci-ence, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmis-sion, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cab-ildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Eu-rope', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University. Author contributions: Q. Zhang, A. Pizzorno, L. Miorin, P., The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH, R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the 'Investments for the Future' program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y De-sarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1, AEI/ FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and 'Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19'). E. Andreakos is supported by the Hellenic Foundation for Research and, Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and In-stituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009), cofinanced by European Regional Development Fund 'A way to achieve Europe', Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University., ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020), ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020), ANR-21-COVR-0039,GenMIS-C,Recherche des Déficits immunitaires innées monogéniques prédisposant au syndrome inflammatoire multisystémique chez l'enfant.(2021), and ANR-21-RHUS-0008,COVIFERON,Covid-19 and interferons: from discovery to therapy(2021)
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INTERFERON ,Cerba HealthCare Group ,Immunology ,SEVERE COVID-19 ,Pneumònia ,Autoanticossos ,DETERMINANTS ,IMMUNITY ,Grip ,NEUTRALIZING ANTIBODIES ,3C-Dijon Study ,INFECTION ,Influenza, Human ,Medicine and Health Sciences ,Immunology and Allergy ,Humans ,COVID Human Genetic Effort ,MYASTHENIA-GRAVIS PATIENTS ,Autoantibodies ,REIPI INF Working Group ,Etablissement Français du Sang Study Group ,Yellow Fever Vaccine ,COVID-19 ,Pneumonia ,ALLELES ,Lyon Antigrippe Working Group ,Influenza ,ALPHA ,Settore MED/03 ,Interferon Type I ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,BURDEN ,Constances Cohort - Abstract
Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients 70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those, The Laboratory of Human Genetics of Infectious Diseases is supported by the Howard Hughes Medical Institute, the Rockefeller University, the St. Giles Foundation, the National Institutes of Health (NIH; R01AI088364 and R01AI163029), the National Center for Advancing Translational Sciences, NIH Clinical and Translational Science Award program (UL1 TR001866), the Fisher Center for Alzheimer’s Research Foundation, the Meyer Foundation, the JPB Foundation, the French National Research Agency (ANR) under the “Investments for the Future” program (ANR-10-IAHU-01), the Integrative Biology of Emerging Infectious Diseases Laboratory of Excellence (ANR-10-LABX-62-IBEID), the French Foundation for Medical Research (EQU201903007798), the ANRS-COV05, ANR-RHU program ANR-21-RHUS-08, ANR GENVIR (ANR-20-CE93-003), ANR GenMISC (ANR-21-COVR-0039), and ANR AABIFNCOV (ANR-20-CO11-0001) projects, the European Union’s Horizon 2020 research and innovation program under grant agreement 824110 (EASI-genomics), the HORIZON-HLTH-2021-DISEASE-04 program under grant agreement 01057100 (UNDINE), the Square Foundation, Grandir–Fonds de solidarité pour l’enfance, the Fondation du Souffle, the SCOR Corporate Foundation for Science, the French Ministry of Higher Education, Research, and Innovation (MESRI-COVID-19), Institut National de la Santé et de la Recherche Médicale (INSERM), REACTing-INSERM, and the Université Paris Cité. This work was partly supported by the Center for Research on Influenza Pathogenesis and Transmission, a National Institute of Allergy and Infectious Diseases (NIAID)–funded Center of Excellence for Influenza Research and Response (contract no. 75N93021C00014), and the FLUOMICS Consortium (NIH-NIAID grant U19AI135972) to both A. García-Sastre and R.A. Medina, and by NIAID grant U19AI142733 and U19AI168631 to A. García-Sastre. Work in the Medina laboratory was also supported by the PIA ACT 1408, FONDECYT 1161971 and 1212023 grants from Agencia Nacional de Investigación y Desarrollo of Chile. The VirPath team is supported by INSERM REACTing (Research & Action Emerging Infectious Diseases), CNRS, and Mérieux Research grants. B. Padey is supported by an ANRT CIFRE PhD scholarship. For the Lyon cohort, specimen collection and study was supported by a grant from the French Ministry of Health PHRC-I 2013 ANTIGRIPPE. C. Rodríguez-Gallego and colleagues were supported by the Instituto de Salud Carlos III (COV20_01333, COV20_01334, and PI12/01565, Spanish Ministry for Science and Innovation RTC-2017-6471-1; AEI/FEDER, UE), Grupo DISA, Fundación MAPFRE Guanarteme, Sociedad Española de Neumología y Cirugía Torácica and Cabildo Insular de Tenerife (CGIEU0000219140 and “Apuestas, científicas del Instituto Tecnológico y de Energías Renovables para colaborar en la lucha contra la COVID-19”). E. Andreakos is supported by the Hellenic Foundation for Research and Innovation (INTERFLU, no. 1574). P. Bastard was supported by the French Foundation for Medical Research (EA20170638020) and by the MD-PhD program of the Imagine Institute (with the support of the Fondation Bettencourt-Schueller). This study was supported by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0009); cofinanced by European Regional Development Fund “A way to achieve Europe”; Operative Program Intelligence Growth 2014-2020 (CB21/13/00006) also was supported by CIBER-Consorcio Centro de Investigación Biomédica en Red, Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea–Next Generation EU and Consejería de Economía, Conocimiento, Empresas y Universidad, Secretaría General de Universidades, Investigación y Tecnología, Junta de Andalucía, Spain (P18-RT-3320). I. Meyts is a Senior Clinical Investigator at the Research Foundation–Flanders and is supported by the CSL Behring Chair of Primary Immunodeficiencies, a CSL-Behring Research Grant, KU Leuven C1 grant C16/18/007, a VIB GC PID Grant, Fonds Wetenschappelijk Onderzoek grants G0C8517N, G0B5120N, and G0E8420N, and the Jeffrey Modell Foundation. Open Access funding provided by Rockefeller University.
- Published
- 2022
13. Autoantibodies against type I IFNs in patients with critical influenza pneumonia.
- Author
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Zhang Q, Pizzorno A, Miorin L, Bastard P, Gervais A, Le Voyer T, Bizien L, Manry J, Rosain J, Philippot Q, Goavec K, Padey B, Cupic A, Laurent E, Saker K, Vanker M, Särekannu K, García-Salum T, Ferres M, Le Corre N, Sánchez-Céspedes J, Balsera-Manzanero M, Carratala J, Retamar-Gentil P, Abelenda-Alonso G, Valiente A, Tiberghien P, Zins M, Debette S, Meyts I, Haerynck F, Castagnoli R, Notarangelo LD, Gonzalez-Granado LI, Dominguez-Pinilla N, Andreakos E, Triantafyllia V, Rodríguez-Gallego C, Solé-Violán J, Ruiz-Hernandez JJ, Rodríguez de Castro F, Ferreres J, Briones M, Wauters J, Vanderbeke L, Feys S, Kuo CY, Lei WT, Ku CL, Tal G, Etzioni A, Hanna S, Fournet T, Casalegno JS, Queromes G, Argaud L, Javouhey E, Rosa-Calatrava M, Cordero E, Aydillo T, Medina RA, Kisand K, Puel A, Jouanguy E, Abel L, Cobat A, Trouillet-Assant S, García-Sastre A, and Casanova JL
- Subjects
- COVID-19 complications, COVID-19 immunology, Humans, Yellow Fever Vaccine adverse effects, Autoantibodies, Influenza, Human complications, Influenza, Human immunology, Interferon Type I immunology, Interferon Type I metabolism, Pneumonia complications, Pneumonia immunology
- Abstract
Autoantibodies neutralizing type I interferons (IFNs) can underlie critical COVID-19 pneumonia and yellow fever vaccine disease. We report here on 13 patients harboring autoantibodies neutralizing IFN-α2 alone (five patients) or with IFN-ω (eight patients) from a cohort of 279 patients (4.7%) aged 6-73 yr with critical influenza pneumonia. Nine and four patients had antibodies neutralizing high and low concentrations, respectively, of IFN-α2, and six and two patients had antibodies neutralizing high and low concentrations, respectively, of IFN-ω. The patients' autoantibodies increased influenza A virus replication in both A549 cells and reconstituted human airway epithelia. The prevalence of these antibodies was significantly higher than that in the general population for patients <70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10-5), but not >70 yr of age (3.1 vs. 4.4%, P = 0.68). The risk of critical influenza was highest in patients with antibodies neutralizing high concentrations of both IFN-α2 and IFN-ω (OR = 11.7, P = 1.3 × 10-5), especially those <70 yr old (OR = 139.9, P = 3.1 × 10-10). We also identified 10 patients in additional influenza patient cohorts. Autoantibodies neutralizing type I IFNs account for ∼5% of cases of life-threatening influenza pneumonia in patients <70 yr old., (© 2022 Zhang et al.)
- Published
- 2022
- Full Text
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