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Autoantibodies neutralizing type I IFNs are present in ~4% of uninfected individuals over 70 years old and account for ~20% of COVID-19 deaths
Science Immunology ( IF 24.8 ) Pub Date : 2021-08-19 , DOI: 10.1126/sciimmunol.abl4340
Paul Bastard 1, 2, 3 , Adrian Gervais 1, 2 , Tom Le Voyer 1, 2 , Jérémie Rosain 1, 2 , Quentin Philippot 1, 2 , Jérémy Manry 1, 2 , Eleftherios Michailidis 4 , Hans-Heinrich Hoffmann 4 , Shohei Eto 5 , Marina Garcia-Prat 6 , Lucy Bizien 1, 2 , Alba Parra-Martínez 6 , Rui Yang 3 , Liis Haljasmägi 7 , Mélanie Migaud 1, 2 , Karita Särekannu 7 , Julia Maslovskaja 7 , Nicolas de Prost 8, 9 , Yacine Tandjaoui-Lambiotte 10 , Charles-Edouard Luyt 11, 12 , Blanca Amador-Borrero 13 , Alexandre Gaudet 14, 15, 16, 17, 18 , Julien Poissy 14, 15, 16, 17, 18 , Pascal Morel 19, 20 , Pascale Richard 19 , Fabrice Cognasse 21, 22 , Jesus Troya 23 , Sophie Trouillet-Assant 24 , Alexandre Belot 25, 26 , Kahina Saker 25 , Pierre Garçon 27 , Jacques G Rivière 6 , Jean-Christophe Lagier 28, 29 , Stéphanie Gentile 30, 31 , Lindsey B Rosen 32 , Elana Shaw 32 , Tomohiro Morio 33 , Junko Tanaka 34 , David Dalmau 35 , Pierre-Louis Tharaux 36 , Damien Sene 13 , Alain Stepanian 37 , Bruno Megarbane 38 , Vasiliki Triantafyllia 39 , Arnaud Fekkar 1, 40 , James R Heath 41 , José Luis Franco 42 , Juan-Manuel Anaya 43 , Jordi Solé-Violán 44, 45 , Luisa Imberti 46 , Andrea Biondi 47 , Paolo Bonfanti 48 , Riccardo Castagnoli 32, 49 , Ottavia M Delmonte 32 , Yu Zhang 32, 50 , Andrew L Snow 51 , Steven M Holland 32 , Catherine Biggs 52 , Marcela Moncada-Vélez 3 , Andrés Augusto Arias 3, 53, 54 , Lazaro Lorenzo 1, 2 , Soraya Boucherit 1, 2 , Boubacar Coulibaly 1, 2 , Dany Anglicheau 55 , Anna M Planas 56, 57 , Filomeen Haerynck 58 , Sotirija Duvlis 59, 60 , Robert L Nussbaum 61 , Tayfun Ozcelik 62 , Sevgi Keles 63 , Ahmed A Bousfiha 64 , Jalila El Bakkouri 64 , Carolina Ramirez-Santana 42, 43 , Stéphane Paul 65 , Qiang Pan-Hammarström 66 , Lennart Hammarström 66 , Annabelle Dupont 67 , Alina Kurolap 68 , Christine N Metz 69 , Alessandro Aiuti 70 , Giorgio Casari 70 , Vito Lampasona 71 , Fabio Ciceri 72 , Lucila A Barreiros 73 , Elena Dominguez-Garrido 74 , Mateus Vidigal 75 , Mayana Zatz 75 , Diederik van de Beek 76 , Sabina Sahanic 77 , Ivan Tancevski 77 , Yurii Stepanovskyy 78 , Oksana Boyarchuk 79 , Yoko Nukui 80 , Miyuki Tsumura 5 , Loreto Vidaur 81, 82 , Stuart G Tangye 83 , Sonia Burrel 84 , Darragh Duffy 85 , Lluis Quintana-Murci 86, 87 , Adam Klocperk 88 , Nelli Y Kann 89 , Anna Shcherbina 89 , Yu-Lung Lau 90 , Daniel Leung 90 , Matthieu Coulongeat 91 , Julien Marlet 92, 93 , Rutger Koning 76 , Luis Felipe Reyes 94, 95 , Angélique Chauvineau-Grenier 96 , Fabienne Venet 97, 98 , Guillaume Monneret 97, 98 , Michel C Nussenzweig 99, 100 , Romain Arrestier 8, 9 , Idris Boudhabhay 55 , Hagit Baris-Feldman 68, 101 , David Hagin 101, 102 , Joost Wauters 103 , Isabelle Meyts 104, 105 , Adam H Dyer 106 , Sean P Kennelly 106 , Nollaig M Bourke 107 , Rabih Halwani 108 , Narjes Saheb Sharif-Askari 108 , Karim Dorgham 109 , Jérome Sallette 110 , Souad Mehlal Sedkaoui 110 , Suzan AlKhater 111, 112 , Raúl Rigo-Bonnin 113 , Francisco Morandeira 114 , Lucie Roussel 115, 116 , Donald C Vinh 115, 116 , Sisse Rye Ostrowski 117 , Antonio Condino-Neto 73 , Carolina Prando 118 , Anastasiia Bonradenko 78 , András N Spaan 3, 119 , Laurent Gilardin 120, 121 , Jacques Fellay 122, 123, 124 , Stanislas Lyonnet 125 , Kaya Bilguvar 126, 127, 128, 129 , Richard P Lifton 126, 127, 130 , Shrikant Mane 127 , , , , , , , , , , , , , , , , , , , , , Mark S Anderson 131 , Bertrand Boisson 1, 2, 3 , Vivien Béziat 1, 2 , Shen-Ying Zhang 1, 2, 3 , Evangelos Vandreakos 132 , Olivier Hermine 2, 133 , Aurora Pujol 134 , Pärt Peterson 7 , Trine H Mogensen 135, 136 , Lee Rowen 41 , James Mond 137 , Stéphanie Debette 138, 139 , Xavier de Lamballerie 140 , Xavier Duval 141, 142, 143, 144 , France Mentré 141, 142, 143 , Marie Zins 145 , Pere Soler-Palacin 6 , Roger Colobran 146 , Guy Gorochov 109, 147 , Xavier Solanich 148 , Sophie Susen 67 , Javier Martinez-Picado 149, 150, 151 , Didier Raoult 28, 29 , Marc Vasse 152 , Peter K Gregersen 69 , Lorenzo Piemonti 71 , Carlos Rodríguez-Gallego 153, 154 , Luigi D Notarangelo 32 , Helen C Su 32, 155 , Kai Kisand 7 , Satoshi Okada 5 , Anne Puel 1, 2, 3 , Emmanuelle Jouanguy 1, 2, 3 , Charles M Rice 4 , Pierre Tiberghien 19, 20 , Qian Zhang 1, 2, 3 , Aurélie Cobat 1, 2, 3 , Laurent Abel 1, 2, 3 , Jean-Laurent Casanova 1, 2, 3, 100
Affiliation  

Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients > 80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4% >80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals <70 years, 2.3% between 70 and 80 years, and 6.3% >80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.



中文翻译:

中和 I 型干扰素的自身抗体存在于约 4% 的 70 岁以上未感染者中,约占 COVID-19 死亡人数的 20%

大约 10% 的重症 COVID-19 肺炎患者中发现了中和高浓度(10 ng/mL,血浆稀释 1 至 10)IFN-α 和/或 -ω 的循环自身抗体 (auto-Abs),但在有无症状感染者。我们检测到,在 3,595 名重症 COVID-19 患者中,有 13.6% 的患者体内的 IFN-α 和/或 -ω 浓度(100 pg/mL,血浆的 1/10 稀释液)浓度降低了 100 倍,且更加生理化。其中包括 374 名 80 岁以上患者中的 21%,以及 522 名重症 COVID-19 患者中的 6.5%。在 1,124 名死亡患者(年龄 20 天至 99 岁;平均:70 岁)中,18% 的人也检测到了这些抗体。此外,另外 1.3% 的重症 COVID-19 患者和 0.9% 的死亡患者具有中和高浓度 IFN-β 的自身抗体。我们还显示,在来自普通人群的 34,159 名未感染受试者的样本中,中和高浓度 IFN-α 和/或 -ω 的自身抗体存在于 18 岁至 69 岁之间的 0.18% 个体中,70 岁至 70 岁之间的个体中存在 1.1%。 79 岁,3.4% >80 岁。此外,在 10,778 名未感染个体的子样本中,携带较低浓度中和自身抗体的受试者比例更大:1% 的个体 <70 岁,2.3% 在 70 至 80 岁之间,6.3% >80 岁。相比之下,中和 IFN-β 的自身抗体不会随着年龄的增长而变得更加频繁。中和 I 型干扰素的自身抗体早于 SARS-CoV-2 感染,并且在 70 岁后患病率急剧上升。他们约占 80 岁以上的危重 COVID-19 病例和总致命 COVID-19 病例的 20%。

更新日期:2021-08-20
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