Browsing by Author "Rosain, Jeremie"

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Open Access
Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children
(Rockefeller University Press, 2024-01-04) Bastard, Paul; Gervais, Adrian; Taniguchi, Maki; Saare, Liisa; Särekannu, Karita; Voyer, Tom le; Philippot, Quentin; Rosain, Jeremie; Bizien, Lucy; Asano, Takaki; Garcia-Prat, Marina; Parra-Martínez, Alba; Migaud, Mélanie; Tsumura, Miyuki; Conti, Francesca; Belot, Alexandre; Rivière, Jacques G.; Morio, Tomohiro; Tanaka, Junko; Javouhey, Etienne; Haerynck, Filomeen; Duvlis, Sotirija; Özçelik, Tayfun; Keles, Sevgi; Redondo, yacine tandjaoui-lambiotte; Escoda, Simon; Husain, Maya; Pan-Hammarström, Qiang; Hammarström, Lennart; Gloria, Ahlijah; Haidar, Anthony ABI; Soudee, Camille; Abolhassani, Hassan; Sahanic, Sabina; Tancevski, Ivan; Nukui, Yoko; Hayakawa, Seiichi; Chrousos, George P.; Michos, Athanasios; Tatsi, Elizabeth; Filippatos, Filippos; Rodriguez-Palmero, Agusti; García, Jesús Troya; Tipu, Imran; Meyts, Isabelle; Roussel, Lucie; Ostrowski, Sisse Rye; Schidlowski, Laire; Prando, Carolina; Condino-Neto, Antonio; Cheikh, Nathalie; Bousfiha, Ahmed Aziz; Bakkouri, Jalila EL; Peterson, Pärt; Pujol, Aurora; Lévy, Romain; Quartier, Pierre; Vinh, Donald C.; Boisson, Bertrand; Béziat, Vivien; Zhang, Shen-Ying; Borghesi, Alessandro; Pession, Andrea; Andreakos, Evangelos; Marr, Nico; Mentis, Alexios-Fotios; Mogensen, Trine Hyrup; Rodríguez-Gallego, Carlos; Soler-Palacín, Pere; Colobran, Roger; Tillmann, Vallo; Neven, Benedicte; Trouillet-Assant, Sophie; Brodin, Petter; Abel, Laurent; Jouanguy, Emmanuelle; Zhang, Qian; Martinon-Torres, Federico; Salas, Antonio; Gómez-Carballa, Alberto; Gonzalez-Granado, Luis Ignacio; Kisand, Kai; Okada, Satoshi; Puel, Anne; Cobat, Aurélie; Casanova, Jean-Laurent
We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2.
Open Access
Human genetic and immunological determinants of critical COVID-19 pneumonia
(Springer Nature, 2022-03-24) Zhang, Qian; Bastard, Paul; Karbuz, Adem; Gervais, Adrian; Tayoun, Ahmad Abou; Aiuti, Alessandro; Belot, Alexandre; Bolze, Alexandre; Gaudet, Alexandre; Bondarenko, Anastasiia; Liu, Zhiyong; Spaan, András N.; Guennoun, Andrea; Arias, Andres Augusto; Planas, Anna M.; Sediva, Anna; Shcherbina, Anna; Neehus, Anna-Lena; Puel, Anne; Froidure, Antoine; Novelli, Antonio; Parlakay, Aslınur Özkaya; Pujol, Aurora; Yahşi, Aysun; Gülhan, Belgin; Bigio, Benedetta; Boisson, Bertrand; Drolet, Beth A.; Franco, Carlos Andres Arango; Flores, Carlos; Rodríguez-Gallego, Carlos; Prando, Carolina; Biggs, Catherine M.; Luyt, Charles-Edouard; Dalgard, Clifton L.; O’Farrelly, Cliona; Matuozzo, Daniela; Dalmau, David; Perlin, David S.; Mansouri, Davood; van de Beek, Diederik; Vinh, Donald C.; Dominguez-Garrido, Elena; Hsieh, Elena W. Y.; Erdeniz, Emine Hafize; Jouanguy, Emmanuelle; Şevketoglu, Esra; Talouarn, Estelle; Quiros-Roldan, Eugenia; Andreakos, Evangelos; Husebye, Eystein; Alsohime, Fahad; Haerynck, Filomeen; Casari, Giorgio; Novelli, Giuseppe; Aytekin, Gökhan; Morelle, Guillaume; Alkan, Gulsum; Bayhan, Gulsum Iclal; Feldman, Hagit Baris; Su, Helen C.; von Bernuth, Horst; Resnick, Igor; Bustos, Ingrid; Meyts, Isabelle; Migeotte, Isabelle; Tancevski, Ivan; Bustamante, Jacinta; Fellay, Jacques; El Baghdadi, Jamila; Martinez-Picado, Javier; Casanova, Jean-Laurent; Rosain, Jeremie; Manry, Jeremy; Chen, Jie; Christodoulou, John; Bohlen, Jonathan; Franco, José Luis; Li, Juan; Anaya, Juan Manuel; Rojas, Julian; Ye, Junqiang; Uddin, K. M. Furkan; Yasar, Kadriye Kart; Kisand, Kai; Okamoto, Keisuke; Chaïbi, Khalil; Mironska, Kristina; Maródi, László; Abel, Laurent; Renia, Laurent; Lorenzo, Lazaro; Hammarström, Lennart; Ng, Lisa F. P.; Quintana-Murci, Lluis; Erazo, Lucia Victoria; Notarangelo, Luigi D.; Reyes, Luis Felipe; Allende, Luis M.; Imberti, Luisa; Renkilaraj, Majistor Raj Luxman Maglorius; Moncada-Velez, Marcela; Materna, Marie; Anderson, Mark S.; Gut, Marta; Chbihi, Marwa; Ogishi, Masato; Emiroglu, Melike; Seppänen, Mikko R. J.; Uddin, Mohammed J.; Shahrooei, Mohammed; Alexander, Natalie; Hatipoglu, Nevin; Marr, Nico; Akçay, Nihal; Boyarchuk, Oksana; Slaby, Ondrej; Akcan, Ozge Metin; Zhang, Peng; Soler-Palacín, Pere; Gregersen, Peter K.; Brodin, Petter; Garçon, Pierre; Morange, Pierre-Emmanuel; Pan-Hammarström, Qiang; Zhou, Qinhua; Philippot, Quentin; Halwani, Rabih; de Diego, Rebeca Perez; Levy, Romain; Yang, Rui; Öz, Şadiye Kübra Tüter; Muhsen, Saleh Al; Kanık-Yüksek, Saliha; Espinosa-Padilla, Sara; Ramaswamy, Sathishkumar; Okada, Satoshi; Bozdemir, Sefika Elmas; Aytekin, Selma Erol; Karabela, Şemsi Nur; Keles, Sevgi; Senoglu, Sevtap; Zhang, Shen-Ying; Duvlis, Sotirija; Constantinescu, Stefan N.; Boisson-Dupuis, Stephanie; Turvey, Stuart E.; Tangye, Stuart G.; Asano, Takaki; Özcelik, Tayfun; Le Voyer, Tom; Maniatis, Tom; Morio, Tomohiro; Mogensen, Trine H.; Sancho-Shimizu, Vanessa; Beziat, Vivien; Solanich, Xavier; Bryceson, Yenan; Lau, Yu-Lung; Itan, Yuval; Cobat, Aurélie; Casanova, Jean-Laurent
SARS-CoV-2 infection is benign in most individuals but, in around 10% of cases, it triggers hypoxaemic COVID-19 pneumonia, which leads to critical illness in around 3% of cases. The ensuing risk of death (approximately 1% across age and gender) doubles every five years from childhood onwards and is around 1.5 times greater in men than in women. Here we review the molecular and cellular determinants of critical COVID-19 pneumonia. Inborn errors of type I interferons (IFNs), including autosomal TLR3 and X-chromosome-linked TLR7 deficiencies, are found in around 1–5% of patients with critical pneumonia under 60 years old, and a lower proportion in older patients. Pre-existing auto-antibodies neutralizing IFNα, IFNβ and/or IFNω, which are more common in men than in women, are found in approximately 15–20% of patients with critical pneumonia over 70 years old, and a lower proportion in younger patients. Thus, at least 15% of cases of critical COVID-19 pneumonia can be explained. The TLR3- and TLR7-dependent production of type I IFNs by respiratory epithelial cells and plasmacytoid dendritic cells, respectively, is essential for host defence against SARS-CoV-2. In ways that can depend on age and sex, insufficient type I IFN immunity in the respiratory tract during the first few days of infection may account for the spread of the virus, leading to pulmonary and systemic inflammation. © 2022, Springer Nature Limited.
Open Access
SARS-CoV-2 brainstem encephalitis in human inherited DBR1 deficiency
(Rockefeller University Press, 2024-07-18) Yi-Hao Chan; Lundberg, Vanja; Pen, Jérémie Le; Yuan, Jiayi; Lee, Danyel; Pinci, Francesca; Volpi, Stefano; Nakajima, Koji; Bondet, Vincent; Linnéa Åkesson, Sanna Emmy; Khobrekar, Noopur; Bodansky, Aaron; Du, Likun; Melander, Tina; Mariaggi, Alice-Andrée; Seeleuthner, Yoann; Saleh, Tariq Shikh; Chakravarty, Debanjana; Marits, Per; Dobbs, Kerry; Vonlanthen, Sofie; Hennings, Viktoria; Thörn, Karolina; Rinchai, Darawan; Bizien, Lucy; Chaldebas, Matthieu; Sobh, Ali; Özçelik, Tayfun; Keles, Sevgi; AlKhater, Suzan; Prando, Carolina; Meyts, Isabelle; Wilson, Michael; Rosain, Jeremie; Jouanguy, Emmanuelle; Aubart, Melodie; Abel, Laurent; Mogensen, Trine Hyrup; Pan-Hammarström, Qiang; Gao, Daxing; Duffy, Darragh; Cobat, Aurélie; Berg, Stefan; Notarangelo, Luigi; Harschnitz, Oliver; Rice, Charles M.; Studer, Lorenz; Casanova, Jean-Laurent; Ekwall, Olov; Zhang, Shen-Ying
Inherited deficiency of the RNA lariat–debranching enzyme 1 (DBR1) is a rare etiology of brainstem viral encephalitis. The cellular basis of disease and the range of viral predisposition are unclear. We report inherited DBR1 deficiency in a 14-year-old boy who suffered from isolated SARS-CoV-2 brainstem encephalitis. The patient is homozygous for a previously reported hypomorphic and pathogenic DBR1 variant (I120T). Consistently, DBR1 I120T/I120T fibroblasts from affected individuals from this and another unrelated kindred have similarly low levels of DBR1 protein and high levels of RNA lariats. DBR1 I120T/I120T human pluripotent stem cell (hPSC)–derived hindbrain neurons are highly susceptible to SARS-CoV-2 infection. Exogenous WT DBR1 expression in DBR1 I120T/I120T fibroblasts and hindbrain neurons rescued the RNA lariat accumulation phenotype. Moreover, expression of exogenous RNA lariats, mimicking DBR1 deficiency, increased the susceptibility of WT hindbrain neurons to SARS-CoV-2 infection. Inborn errors of DBR1 impair hindbrain neuron–intrinsic antiviral immunity, predisposing to viral infections of the brainstem, including that by SARS-CoV-2.