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Author: search.filters.author.Casanova, Jean-Laurent

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    Autoantibodies neutralizing type I IFNs are present in similar to 4\% of uninfected individuals over 70 years old and account for similar to 20\% of COVID-19 deaths
    (AMER ASSOC ADVANCEMENT SCIENCE, 2021-01-01) Bastard, Paul; Gervais, Adrian; Le Voyer, Tom; Rosain, Jeremie; Philippot, Quentin; Manry, Jeremy; Michailidis, Eleftherios; Hoffmann, Hans-Heinrich; Eto, Shohei; Garcia-Prat, Marina; Bizien, Lucy; Parra-Martinez, Alba; Yang, Rui; Haljasmagi, Liis; Migaud, Melanie; Sarekannu, Karita; Maslovskaja, Julia; de Prost, Nicolas; Tandjaoui-Lambiotte, Yacine; Luyt, Charles-Edouard; Amador-Borrero, Blanca; Gaudet, Alexandre; Poissy, Julien; Morel, Pascal; Richard, Pascale; Cognasse, Fabrice; Troya, Jesus; Trouillet-Assant, Sophie; Belot, Alexandre; Saker, Kahina; Garcon, Pierre; Riviere, Jacques G.; Lagier, Jean-Christophe; Gentile, Stephanie; Rosen, Lindsey B.; Shaw, Elana; Morio, Tomohiro; Tanaka, Junko; Dalmau, David; Tharaux, Pierre-Louis; Sene, Damien; Stepanian, Alain; Megarbane, Bruno; Triantafyllia, Vasiliki; Fekkar, Arnaud; Heath, James R.; Franco, Jose Luis; Anaya, Juan-Manuel; Sole-Violan, Jordi; Imberti, Luisa; Biondi, Andrea; Bonfanti, Paolo; Castagnoli, Riccardo; Delmonte, Ottavia M.; Zhang, Yu; Snow, Andrew L.; Holland, Steven M.; Biggs, Catherine M.; Moncada-Velez, Marcela; Arias, Andres Augusto; Lorenzo, Lazaro; Boucherit, Soraya; Coulibaly, Boubacar; Anglicheau, Dany; Planas, Anna M.; Haerynck, Filomeen; Duvlis, Sotirija; Nussbaum, Robert L.; Ozcelik, Tayfun; Keles, Sevgi; Bousfiha, Ahmed A.; El Bakkouri, Jalila; Ramirez-Santana, Carolina; Paul, Stephane; Pan-Hammarstrom, Qiang; Hammarstrom, Lennart; Dupont, Annabelle; Kurolap, Alina; Metz, Christine N.; Aiuti, Alessandro; Casari, Giorgio; Lampasona, Vito; Ciceri, Fabio; Barreiros, Lucila A.; Dominguez-Garrido, Elena; Vidigal, Mateus; Zatz, Mayana; van de Beek, Diederik; Sahanic, Sabina; Tancevski, Ivan; Stepanovskyy, Yurii; Boyarchuk, Oksana; Nukui, Yoko; Tsumura, Miyuki; Vidaur, Loreto; Tangye, Stuart G.; Burrel, Sonia; Duffy, Darragh; Quintana-Murci, Lluis; Klocperk, Adam; Kann, Nelli Y.; Shcherbina, Anna; Lau, Yu-Lung; Leung, Daniel; Coulongeat, Matthieu; Marlet, Julien; Koning, Rutger; Reyes, Luis Felipe; Chauvineau-Grenier, Angelique; Venet, Fabienne; Monneret, Guillaume; Nussenzweig, Michel C.; Arrestier, Romain; Boudhabhay, Idris; Baris-Feldman, Hagit; Hagin, David; Wauters, Joost; Meyts, Isabelle; Dyer, Adam H.; Kennelly, Sean P.; Bourke, Nollaig M.; Halwani, Rabih; Sharif-Askari, Narjes Saheb; Dorgham, Karim; Sallette, Jerome; Sedkaoui, Souad Mehlal; AlKhater, Suzan; Rigo-Bonnin, Raul; Morandeira, Francisco; Roussel, Lucie; Vinh, Donald C.; Ostrowski, Sisse Rye; Condino-Neto, Antonio; Prando, Carolina; Bondarenko, Anastasiia; Spaan, Andras N.; Gilardin, Laurent; Fellay, Jacques; Lyonnet, Stanislas; Bilguvar, Kaya; Lifton, Richard P.; Mane, Shrikant; Anderson, Mark S.; Boisson, Bertrand; Beziat, Vivien; Zhang, Shen-Ying; Andreakos, Evangelos; Hermine, Olivier; Pujol, Aurora; Peterson, Part; Mogensen, Trine H.; Rowen, Lee; Mond, James; Debette, Stephanie; de Lamballerie, Xavier; Duval, Xavier; Mentre, France; Zins, Marie; Soler-Palacin, Pere; Colobran, Roger; Gorochov, Guy; Solanich, Xavier; Susen, Sophie; Martinez-Picado, Javier; Raoult, Didier; Vasse, Marc; Gregersen, Peter K.; Piemonti, Lorenzo; Rodriguez-Gallego, Carlos; Notarangelo, Luigi D.; Su, Helen C.; Kisand, Kai; Okada, Satoshi; Puel, Anne; Jouanguy, Emmanuelle; Rice, Charles M.; Tiberghien, Pierre; Zhang, Qian; Cobat, Aurelie; Abel, Laurent; Casanova, Jean-Laurent; Lab, H. G. I. D.; Clinicians, C. O. V. I. D.; Clinicians, C. O. V. I. D.-S. T. O. R. M.; Grp, N.I.A.I.D. Immune Response Covid; Grp, N. H.-C.O.V.A.I.R. Study; Danish, C. H. G. E.; Study, Danish Blood Donor; Interest, St Jamess Hosp Sars CoV2; Grp, French C.O.V.I.D. Cohort Study; COVID-Grp, Imagine; Consortium, Milieu Interieur; Cohort, CoV-Contact; Inv, Amsterdam Umc Covid-19 Biobank; Efft, C.O.V.I.D. Human Genetic; Cohort, C. O. N. S. T. A. N. C. E. S.; Study, 3C.-Dijon; HealthCare, Cerba; Grp, Etab Sang Study
    Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/ml
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    The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies
    (NATL ACAD SCIENCES, 2022-01-01) Manry, Jeremy; Bastard, Paul; Gervais, Adrian; Le Voyer, Tom; Rosain, Jeremie; Philippot, Quentin; Michailidis, Eleftherios; Hoffmann, Hans-Heinrich; Eto, Shohei; Garcia-Prat, Marina; Bizien, Lucy; Parra-Martinez, Alba; Yang, Rui; Haljasmagi, Liis; Migaud, Melanie; Sarekannu, Karita; Maslovskaja, Julia; de Prost, Nicolas; Tandjaoui-Lambiotte, Yacine; Luyt, Charles-Edouard; Amador-Borrero, Blanca; Gaudet, Alexandre; Poissy, Julien; Morel, Pascal; Richard, Pascale; Cognasse, Fabrice; Troya, Jesus; Trouillet-Assant, Sophie; Belot, Alexandre; Saker, Kahina; Garcon, Pierre; Riviere, Jacques G.; Lagier, Jean-Christophe; Gentile, Stephanie; Rosen, Lindsey B.; Shaw, Elana; Morio, Tomohiro; Tanaka, Junko; Dalmau, David; Tharaux, Pierre-Louis; Sene, Damien; Stepanian, Alain; Megarbane, Bruno; Triantafyllia, Vasiliki; Fekkar, Arnaud; Heath, James R.; Franco, Jose Luis; Anaya, Juan-Manuel; Sole-Violan, Jordi; Imberti, Luisa; Biondi, Andrea; Bonfanti, Paolo; Castagnoli, Riccardo; Delmonte, Ottavia M.; Zhang, Yu; Snow, Andrew L.; Holland, Steven M.; Biggs, Catherine M.; Moncada-Velez, Marcela; Arias, Andres Augusto; Lorenzo, Lazaro; Boucherit, Soraya; Anglicheau, Dany; Planas, Anna M.; Haerynck, Filomeen; Duvlis, Sotirija; Ozcelik, Tayfun; Keles, Sevgi; Bousfiha, Ahmed A.; El Bakkouri, Jalila; Ramirez-Santana, Carolina; Paul, Stephane; Pan-Hammarstrom, Qiang; Hammarstrom, Lennart; Dupont, Annabelle; Kurolap, Alina; Metz, Christine N.; Aiuti, Alessandro; Casari, Giorgio; Lampasona, Vito; Ciceri, Fabio; Barreiros, Lucila A.; Dominguez-Garrido, Elena; Vidigal, Mateus; Zatz, Mayana; van de Beek, Diederik; Sahanic, Sabina; Tancevski, Ivan; Stepanovskyy, Yurii; Boyarchuk, Oksana; Nukui, Yoko; Tsumura, Miyuki; Vidaur, Loreto; Tangye, Stuart G.; Burrel, Sonia; Duffy, Darragh; Quintana-Murci, Lluis; Klocperk, Adam; Kann, Nelli Y.; Shcherbina, Anna; Lau, Yu-Lung; Leung, Daniel; Coulongeat, Matthieu; Marlet, Julien; Koning, Rutger; Reyes, Luis Felipe; Chauvineau-Grenier, Angelique; Venet, Fabienne; Monneret, Guillaume; Nussenzweig, Michel C.; Arrestier, Romain; Boudhabhay, Idris; Baris-Feldman, Hagit; Hagin, David; Wauters, Joost; Meyts, Isabelle; Dyer, Adam H.; Kennelly, Sean; Bourkeh, Nollaig M.; Halwan, Rabih; Sharif-Askar, Fatemeh Saheb; Dorgham, Karim; Sallette, Jerome; Sedkaoui, Souad Mehlal; AlKhater, Suzan; Rigo-Bonnin, Raul; Morandeira, Francisco; Roussel, Lucie; Vinh, Donald C.; Erikstrup, Christian; Condino-Neto, Antonio; Prando, Carolina; Bondarenko, Anastasiia; Spaan, Andras N.; Gilardin, Laurent; Fellay, Jacques; Lyonnet, Stanislas; Bilguvar, Kaya; Lifton, Richard P.; Mane, Shrikant; Anderson, Mark S.; Boisson, Bertrand; Beziat, Vivien; Zhang, Shen-Ying; Andreakos, Evangelos; Hermine, Olivier; Pujol, Aurora; Peterson, Part; Mogensen, Trine H.; Rowen, Lee; Mond, James; Debette, Stephanie; de Lamballerie, Xavier; Burdet, Charles; Bouadma, Lila; Zins, Marie; Soler-Palacin, Pere; Colobran, Roger; Gorochov, Guy; Solanich, Xavier; Susen, Sophie; Martinez-Picado, Javier; Raoult, Didier; Vasse, Marc; Gregersen, Peter K.; Piemonti, Lorenzo; Rodriguez-Gallego, Carlos; D Notarangelo, Luigi; Su, Helen C.; Kisand, Kai; Okada, Satoshi; Puel, Anne; Jouanguy, Emmanuelle; Rice, Charles M.; Tiberghien, Pierre; Zhang, Qian; Casanova, Jean-Laurent; Abel, Laurent; Cobat, Aurelie; Lab, H. G. I. D.; Clinicians, C. O. V. I. D.; Clinicians, C. O. V. I. D.-S. T. O. R. M.; Grp, N.I.A.I.D. Immune Response C. O. V. I. D.; Grp, N. H.-C.O.V.A.I.R. Study; Danish, C. H. G. E.; Study, Danish Blood Donor; Hosp, St Jamess; Grp, French C.O.V.I.D. Cohort Study; COVID-Grp, Imagine; Consortium, Milieu Interieur; Cohort, CoV-Contact; Biobank, Amsterdam U.M.C. Covid-19; Effort, C.O.V.I.D. Human Genetic; Grp, C. P.-C. O. V. I. D.-19; Cohort, C. O. N. S. T. A. N. C. E. S.; Study, 3C.-Dijon; Hlth-Care, Cerba; Grp, Etab Francais Sang Study
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fatality rate (IFR) doubles with every 5 y of age from childhood onward. Circulating autoantibodies neutralizing IFN-alpha, IFN-omega, and/or IFN-beta are found in similar to 20\% of deceased patients across age groups, and in similar to 1\% of individuals aged <70 y and in >4\% of those >70 y old in the general population. With a sample of 1,261 unvaccinated deceased patients and 34,159 individuals of the general population sampled before the pandemic, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to noncarriers. The RRD associated with any combination of autoantibodies was higher in subjects under 70 y old. For autoantibodies neutralizing IFN-alpha 2 or IFN-omega, the RRDs were 17.0 (95\% CI: 11.7 to 24.7) and 5.8 (4.5 to 7.4) for individuals <70 y and >= 70 y old, respectively, whereas, for autoantibodies neutralizing both molecules, the RRDs were 188.3 (44.8 to 774.4) and 7.2 (5.0 to 10.3), respectively. In contrast, IFRs increased with age, ranging from 0.17\% (0.12 to 0.31) for individuals <40 y old to 26.7\% (20.3 to 35.2) for those >= 80 y old for autoantibodies neutralizing IFN-alpha 2 or IFN-omega, and from 0.84\% (0.31 to 8.28) to 40.5\% (27.82 to 61.20) for autoantibodies neutralizing both. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, especially when neutralizing both IFN-alpha 2 and IFN-omega. Remarkably, IFRs increase with age, whereas RRDs decrease with age. Autoimmunity to type I IFNs is a strong and common predictor of COVID-19 death.
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    The genetic structure of the Turkish population reveals high levels of variation and admixture
    (NATL ACAD SCIENCES, 2021-01-01) Kars, M. Ece; Basak, A. Nazli; Onat, O. Emre; Bilguvar, Kaya; Choi, Jungmin; Itan, Yuval; Caglar, Caner; Palvadeau, Robin; Casanova, Jean-Laurent; Cooper, David N.; Stenson, Peter D.; Yavuz, Alper; Bulus, Hakan; Gunel, Murat; Friedman, Jeffrey M.; Ozcelik, Tayfun
    The construction of population-based variomes has contributed substantially to our understanding of the genetic basis of human inherited disease. Here, we investigated the genetic structure of Turkey from 3,362 unrelated subjects whose whole exomes (n = 2,589) or whole genomes (n = 773) were sequenced to generate a Turkish (TR) Variome that should serve to facilitate disease gene discovery in Turkey. Consistent with the history of present-day Turkey as a crossroads between Europe and Asia, we found extensive admixture between Balkan, Caucasus, Middle Eastern, and European populations with a closer genetic relationship of the TR population to Europeans than hitherto appreciated. We determined that 50\% of TR individuals had high inbreeding coefficients (>= 0.0156) with runs of homozygosity longer than 4 Mb being found exclusively in the TR population when compared to 1000 Genomes Project populations. We also found that 28\% of exome and 49\% of genome variants in the very rare range (allele frequency < 0.005) are unique to the modern TR population. We annotated these variants based on their functional consequences to establish a TR Variome containing alleles of potential medical relevance, a repository of homozygous loss-of-function variants and a TR reference panel for genotype imputation using high-quality haplotypes, to facilitate genome-wide association studies. In addition to providing information on the genetic structure of the modern TR population, these data provide an invaluable resource for future studies to identify variants that are associated with specific phenotypes as well as establishing the phenotypic consequences of mutations in specific genes.