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Article ; Online: Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia.

Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research

2023 Volume 43, Issue 9, Page(s) 379–393

Abstract: Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients ...

Abstract	Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06;
MeSH term(s)	Humans ; COVID-19 ; Interferon Lambda ; SARS-CoV-2 ; Autoantibodies ; Interferon-alpha ; Interferon Type I ; Interferons
Chemical Substances	Interferon Lambda ; Autoantibodies ; Interferon-alpha ; Interferon Type I ; Interferons (9008-11-1)
Language	English
Publishing date	2023-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1226675-9
ISSN	1557-7465 ; 1079-9907
ISSN (online)	1557-7465
ISSN	1079-9907
DOI	10.1089/jir.2023.0003
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Article ; Online: Inactive disease in patients with lupus is linked to autoantibodies to type I interferons that normalize blood IFNα and B cell subsets.

Bradford, Hannah F / Haljasmägi, Liis / Menon, Madhvi / McDonnell, Thomas C R / Särekannu, Karita / Vanker, Martti / Peterson, Pärt / Wincup, Chris / Abida, Rym / Gonzalez, Raquel Fernandez / Bondet, Vincent / Duffy, Darragh / Isenberg, David A / Kisand, Kai / Mauri, Claudia

Cell reports. Medicine

2022 Volume 4, Issue 1, Page(s) 100894

Abstract: Systemic lupus erythematosus (SLE) is characterized by increased expression of type I interferon (IFN)-regulated genes in 50%-75% of patients. We report that out of 501 patients with SLE analyzed, 73 (14%) present autoantibodies against IFNα (anti-IFN- ... ...

Abstract	Systemic lupus erythematosus (SLE) is characterized by increased expression of type I interferon (IFN)-regulated genes in 50%-75% of patients. We report that out of 501 patients with SLE analyzed, 73 (14%) present autoantibodies against IFNα (anti-IFN-Abs). The presence of neutralizing-anti-IFN-Abs in 4.2% of patients inversely correlates with low circulating IFNα protein levels, inhibition of IFN-I downstream gene signatures, and inactive global disease score. Hallmarks of SLE pathogenesis, including increased immature, double-negative plasmablast B cell populations and reduction in regulatory B cell (Breg) frequencies, were normalized in patients with neutralizing anti-IFN-Abs compared with other patient groups. Immunoglobulin G (IgG) purified from sera of patients with SLE with neutralizing anti-IFN-Abs impedes CpGC-driven IFNα-dependent differentiation of B cells into immature B cells and plasmablasts, thus recapitulating the neutralizing effect of anti-IFN-Abs on B cell differentiation in vitro. Our findings highlight a role for neutralizing anti-IFN-Abs in controlling SLE pathogenesis and support the use of IFN-targeting therapies in patients with SLE lacking neutralizing-anti-IFN-Abs.
MeSH term(s)	Humans ; Interferon Type I ; Autoantibodies ; B-Lymphocyte Subsets/metabolism ; Interferon-alpha/therapeutic use ; Interferon-alpha/genetics ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/genetics
Chemical Substances	Interferon Type I ; Autoantibodies ; Interferon-alpha
Language	English
Publishing date	2022-07-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2022.100894
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Article ; Online: Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children.

Bastard, Paul / Gervais, Adrian / Taniguchi, Maki / Saare, Liisa / Särekannu, Karita / Le Voyer, Tom / Philippot, Quentin / Rosain, Jérémie / 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 / Ozcelik, Tayfun / Keles, Sevgi / Tandjaoui-Lambiotte, Yacine / Escoda, Simon / Husain, Maya / Pan-Hammarström, Qiang / Hammarström, Lennart / Ahlijah, Gloria / Abi Haidar, Anthony / Soudee, Camille / Arseguel, Vincent / Abolhassani, Hassan / Sahanic, Sabina / Tancevski, Ivan / Nukui, Yoko / Hayakawa, Seiichi / Chrousos, George P / Michos, Athanasios / Tatsi, Elizabeth-Barbara / Filippatos, Filippos / Rodriguez-Palmero, Agusti / Troya, Jesus / Tipu, Imran / Meyts, Isabelle / Roussel, Lucie / Ostrowski, Sisse Rye / Schidlowski, Laire / Prando, Carolina / Condino-Neto, Antonio / Cheikh, Nathalie / Bousfiha, Ahmed A / El Bakkouri, Jalila / 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 A / Mogensen, Trine H / Rodríguez-Gallego, Carlos / Soler-Palacin, Pere / Colobran, Roger / Tillmann, Vallo / Neven, Bénédicte / Trouillet-Assant, Sophie / Brodin, Petter / Abel, Laurent / Jouanguy, Emmanuelle / Zhang, Qian / Martinón-Torres, Federico / Salas, Antonio / Gómez-Carballa, Alberto / Gonzalez-Granado, Luis I / Kisand, Kai / Okada, Satoshi / Puel, Anne / Cobat, Aurélie / Casanova, Jean-Laurent

The Journal of experimental medicine

2024 Volume 221, Issue 2

Abstract: We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; ...

Abstract	We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω 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-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-ω 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-ω and/or IFN-α2.
MeSH term(s)	Child ; Humans ; COVID-19 ; Interferon-alpha ; Interferon Type I ; Autoantibodies
Chemical Substances	Interferon-alpha ; Interferon Type I ; Autoantibodies
Language	English
Publishing date	2024-01-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20231353
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Article ; Online: Autoantibodies against type I IFNs in patients with critical influenza pneumonia.

Zhang, Qian / Pizzorno, Andrés / Miorin, Lisa / Bastard, Paul / Gervais, Adrian / Le Voyer, Tom / Bizien, Lucy / Manry, Jeremy / Rosain, Jérémie / Philippot, Quentin / Goavec, Kelian / Padey, Blandine / Cupic, Anastasija / Laurent, Emilie / Saker, Kahina / Vanker, Martti / Särekannu, Karita / García-Salum, Tamara / Ferres, Marcela /

Le Corre, Nicole / Sánchez-Céspedes, Javier / Balsera-Manzanero, María / Carratala, Jordi / Retamar-Gentil, Pilar / Abelenda-Alonso, Gabriela / Valiente, Adoración / Tiberghien, Pierre / Zins, Marie / Debette, Stéphanie / Meyts, Isabelle / Haerynck, Filomeen / Castagnoli, Riccardo / Notarangelo, Luigi D / Gonzalez-Granado, Luis I / Dominguez-Pinilla, Nerea / Andreakos, Evangelos / Triantafyllia, Vasiliki / Rodríguez-Gallego, Carlos / Solé-Violán, Jordi / Ruiz-Hernandez, José Juan / Rodríguez de Castro, Felipe / Ferreres, José / Briones, Marisa / Wauters, Joost / Vanderbeke, Lore / Feys, Simon / Kuo, Chen-Yen / Lei, Wei-Te / Ku, Cheng-Lung / Tal, Galit / Etzioni, Amos / Hanna, Suhair / Fournet, Thomas / Casalegno, Jean-Sebastien / Queromes, Gregory / Argaud, Laurent / Javouhey, Etienne / Rosa-Calatrava, Manuel / Cordero, Elisa / Aydillo, Teresa / Medina, Rafael A / Kisand, Kai / Puel, Anne / Jouanguy, Emmanuelle / Abel, Laurent / Cobat, Aurélie / Trouillet-Assant, Sophie / García-Sastre, Adolfo / Casanova, Jean-Laurent

The Journal of experimental medicine

2022 Volume 219, Issue 11

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 ... ...

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.
MeSH term(s)	Autoantibodies ; COVID-19/complications ; COVID-19/immunology ; Humans ; Influenza, Human/complications ; Influenza, Human/immunology ; Interferon Type I/immunology ; Interferon Type I/metabolism ; Pneumonia/complications ; Pneumonia/immunology ; Yellow Fever Vaccine/adverse effects
Chemical Substances	Autoantibodies ; Interferon Type I ; Yellow Fever Vaccine
Language	English
Publishing date	2022-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20220514
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Article: The risk of COVID-19 death is much greater and age-dependent with type I IFN autoantibodies.

Manry, Jeremy / Bastard, Paul / Gervais, Adrian / Le Voyer, Tom / Rosain, Jérémie / Philippot, Quentin / Michailidis, Eleftherios / Hoffmann, Hans-Heinrich / Eto, Shohei / Garcia-Prat, Marina / Bizien, Lucy / Parra-Martínez, Alba / Yang, Rui / Haljasmägi, Liis / Migaud, Mélanie / Särekannu, 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 / Garçon, Pierre / Rivière, Jacques G / Lagier, Jean-Christophe / Gentile, Stéphanie / Rosen, Lindsey / Shaw, Elana / Morio, Tomohiro / Tanaka, Junko / Dalmau, David / Tharaux, Pierre-Louis / Sene, Damien / Stepanian, Alain / Mégarbane, Bruno / Triantafyllia, Vasiliki / Fekkar, Arnaud / Heath, James / Franco, Jose / Anaya, Juan-Manuel / Solé-Violán, Jordi / Imberti, Luisa / Biondi, Andrea / Bonfanti, Paolo / Castagnoli, Riccardo / Delmonte, Ottavia / Zhang, Yu / Snow, Andrew / Holland, Steve / Biggs, Catherine / Moncada-Vélez, Marcela / Arias, Andrés / Lorenzo, Lazaro / Boucherit, Soraya / Anglicheau, Dany / Planas, Anna / Haerynck, Filomeen / Duvlis, Sotirija / Nussbaum, Robert / Ozcelik, Tayfun / Keles, Sevgi / Bousfiha, Aziz / El Bakkouri, Jalila / Ramirez-Santana, Carolina / Paul, Stéphane / Pan-Hammarstrom, Qiang / Hammarstrom, Lennart / Dupont, Annabelle / Kurolap, Alina / Metz, Christine / Aiuti, Alessandro / Casari, Giorgio / Lampasona, Vito / Ciceri, Fabio / Barreiros, Lucila / 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 / Burrel, Sonia / Duffy, Darragh / Quintana-Murci, Lluis / Klocperk, Adam / Kann, Nelli / Shcherbina, Anna / Lau, Yu-Lung / Leung, Daniel / Coulongeat, Matthieu / Marlet, Julien / Koning, Rutger / Reyes, Luis / Chauvineau-Grenier, Angélique / Venet, Fabienne / Monneret, Guillaume / Nussenzweig, Michel / Arrestier, Romain / Boudhabhay, Idris / Baris-Feldman, Hagit / Hagin, David / Wauters, Joost / Meyts, Isabelle / Dyer, Adam / Kennelly, Sean / Bourke, Nollaig / Halwani, Rabih / Sharif-Askari, Fatemeh / Dorgham, Karim / Sallette, Jérôme / Mehlal-Sedkaoui, Souad / AlKhater, Suzan / Rigo-Bonnin, Raúl / Morandeira, Francisco / Roussel, Lucie / Vinh, Donald / Erikstrup, Christian / Condino-Neto, Antonio / Prando, Carolina / Bondarenko, Anastasiia / Spaan, András / Gilardin, Laurent / Fellay, Jacques / Lyonnet, Stanislas / Bilguvar, Kaya / Lifton, Richard / Mane, Shrikant / Anderson, Mark / Boisson, Bertrand / Béziat, Vivien / Zhang, Shen-Ying / Andreakos, Evangelos / Hermine, Olivier / Pujol, Aurora / Peterson, Pärt / Mogensen, Trine Hyrup / Rowen, Lee / Mond, James / Debette, Stéphanie / deLamballerie, 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 / Rodríguez-Gallego, Carlos / Piemonti, Lorenzo / Notarangelo, Luigi / Su, Helen / Kisand, Kai / Okada, Satoshi / Puel, Anne / Jouanguy, Emmanuelle / Rice, Charles / Tiberghien, Pierre / Zhang, Qian / Casanova, Jean-Laurent / Abel, Laurent / Cobat, Aurélie

Research square

2022

Abstract: SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, ... ...

Abstract	SARS-CoV-2 infection fatality rate (IFR) doubles with every five years of age from childhood onward. Circulating autoantibodies neutralizing IFN-α, IFN-ω, and/or IFN-β are found in ~20% of deceased patients across age groups. In the general population, they are found in ~1% of individuals aged 20-70 years and in >4% of those >70 years old. With a sample of 1,261 deceased patients and 34,159 uninfected individuals, we estimated both IFR and relative risk of death (RRD) across age groups for individuals carrying autoantibodies neutralizing type I IFNs, relative to non-carriers. For autoantibodies neutralizing IFN-α2 or IFN-ω, the RRD was 17.0[95% CI:11.7-24.7] for individuals under 70 years old and 5.8[4.5-7.4] for individuals aged 70 and over, whereas, for autoantibodies neutralizing both molecules, the RRD was 188.3[44.8-774.4] and 7.2[5.0-10.3], respectively. IFRs increased with age, from 0.17%[0.12-0.31] for individuals <40 years old to 26.7%[20.3-35.2] for those ≥80 years old for autoantibodies neutralizing IFN-α2 or IFN-ω, and from 0.84%[0.31-8.28] to 40.5%[27.82-61.20] for the same two age groups, for autoantibodies neutralizing both molecules. Autoantibodies against type I IFNs increase IFRs, and are associated with high RRDs, particularly those neutralizing both IFN-α2 and -ω. Remarkably, IFR increases with age, whereas RRD decreases with age. Autoimmunity to type I IFNs appears to be second only to age among common predictors of COVID-19 death.
Language	English
Publishing date	2022-01-14
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-1225906/v1
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Article ; Online: The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

Manry, Jérémy / Bastard, Paul / Gervais, Adrian / Le Voyer, Tom / Rosain, Jérémie / Philippot, Quentin / Michailidis, Eleftherios / Hoffmann, Hans-Heinrich / Eto, Shohei / Garcia-Prat, Marina / Bizien, Lucy / Parra-Martínez, Alba / Yang, Rui / Haljasmägi, Liis / Migaud, Mélanie / Särekannu, 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, Jesús / Trouillet-Assant, Sophie / Belot, Alexandre / Saker, Kahina / Garçon, Pierre / Rivière, Jacques G / Lagier, Jean-Christophe / Gentile, Stéphanie / Rosen, Lindsey B / Shaw, Elana / Morio, Tomohiro / Tanaka, Junko / Dalmau, David / Tharaux, Pierre-Louis / Sene, Damien / Stepanian, Alain / Mégarbane, Bruno / Triantafyllia, Vasiliki / Fekkar, Arnaud / Heath, James R / Franco, José Luis / Anaya, Juan-Manuel / Solé-Violán, Jordi / Imberti, Luisa / Biondi, Andrea / Bonfanti, Paolo / Castagnoli, Riccardo / Delmonte, Ottavia M / Zhang, Yu / Snow, Andrew L / Holland, Steven M / Biggs, Catherine M / Moncada-Vélez, Marcela / Arias, Andrés 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, Stéphane / Pan-Hammarström, Qiang / Hammarström, 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, Angélique / 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, Fatemeh Saheb / Dorgham, Karim / Sallette, Jérôme / Sedkaoui, Souad Mehlal / AlKhater, Suzan / Rigo-Bonnin, Raúl / Morandeira, Francisco / Roussel, Lucie / Vinh, Donald C / Erikstrup, Christian / Condino-Neto, Antonio / Prando, Carolina / Bondarenko, Anastasiia / Spaan, András N / Gilardin, Laurent / Fellay, Jacques / Lyonnet, Stanislas / Bilguvar, Kaya / Lifton, Richard P / Mane, Shrikant / Anderson, Mark S / Boisson, Bertrand / Béziat, Vivien / Zhang, Shen-Ying / Andreakos, Evangelos / Hermine, Olivier / Pujol, Aurora / Peterson, Pärt / Mogensen, Trine H / Rowen, Lee / Mond, James / Debette, Stéphanie / 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 / Rodríguez-Gallego, Carlos / Notarangelo, Luigi D / Su, Helen C / Kisand, Kai / Okada, Satoshi / Puel, Anne / Jouanguy, Emmanuelle / Rice, Charles M / Tiberghien, Pierre / Zhang, Qian / Casanova, Jean-Laurent / Abel, Laurent / Cobat, Aurélie

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 21, Page(s) e2200413119

Abstract: 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-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients ... ...

Abstract	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-α, IFN-ω, and/or IFN-β are found in ∼20% of deceased patients across age groups, and in ∼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-α2 or IFN-ω, 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-α2 or IFN-ω, 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-α2 and IFN-ω. 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.
MeSH term(s)	Adult ; Age Factors ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/blood ; Autoantibodies/blood ; Autoimmunity ; COVID-19/immunology ; COVID-19/mortality ; Female ; Humans ; Interferon Type I/immunology ; Male ; Middle Aged ; Risk ; SARS-CoV-2
Chemical Substances	Antibodies, Neutralizing ; Autoantibodies ; Interferon Type I
Language	English
Publishing date	2022-05-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2200413119
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Autoantibodies neutralizing type I IFNs are present in

Bastard, Paul / Gervais, Adrian / Le Voyer, Tom / Rosain, Jérémie / Philippot, Quentin / Manry, Jérémy / Michailidis, Eleftherios / Hoffmann, Hans-Heinrich / Eto, Shohei / Garcia-Prat, Marina / Bizien, Lucy / Parra-Martínez, Alba / Yang, Rui / Haljasmägi, Liis / Migaud, Mélanie / Särekannu, 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 / Garçon, Pierre / Rivière, Jacques G / Lagier, Jean-Christophe / Gentile, Stéphanie / 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, José Luis / Anaya, Juan-Manuel / Solé-Violán, Jordi / Imberti, Luisa / Biondi, Andrea / Bonfanti, Paolo / Castagnoli, Riccardo / Delmonte, Ottavia M / Zhang, Yu / Snow, Andrew L / Holland, Steven M / Biggs, Catherine / Moncada-Vélez, Marcela / Arias, Andrés 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, Stéphane / Pan-Hammarström, Qiang / Hammarström, 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, Angélique / 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, Jérome / Sedkaoui, Souad Mehlal / AlKhater, Suzan / Rigo-Bonnin, Raúl / Morandeira, Francisco / Roussel, Lucie / Vinh, Donald C / Ostrowski, Sisse Rye / Condino-Neto, Antonio / Prando, Carolina / Bonradenko, Anastasiia / Spaan, András N / Gilardin, Laurent / Fellay, Jacques / Lyonnet, Stanislas / Bilguvar, Kaya / Lifton, Richard P / Mane, Shrikant / Anderson, Mark S / Boisson, Bertrand / Béziat, Vivien / Zhang, Shen-Ying / Vandreakos, Evangelos / Hermine, Olivier / Pujol, Aurora / Peterson, Pärt / Mogensen, Trine H / Rowen, Lee / Mond, James / Debette, Stéphanie / de Lamballerie, Xavier / Duval, Xavier / Mentré, 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 / Rodríguez-Gallego, Carlos / Notarangelo, Luigi D / Su, Helen C / Kisand, Kai / Okada, Satoshi / Puel, Anne / Jouanguy, Emmanuelle / Rice, Charles M / Tiberghien, Pierre / Zhang, Qian / Cobat, Aurélie / Abel, Laurent / Casanova, Jean-Laurent

Science immunology

2019 Volume 6, Issue 62

Abstract: 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 ... ...

Abstract	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.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Autoantibodies/blood ; Autoantibodies/immunology ; COVID-19/immunology ; COVID-19/mortality ; Case-Control Studies ; Child ; Child, Preschool ; Critical Illness ; Humans ; Immunoglobulin G/blood ; Immunoglobulin G/immunology ; Infant ; Infant, Newborn ; Interferon Type I/immunology ; Interferon-alpha/immunology ; Middle Aged ; Young Adult
Chemical Substances	Antibodies, Neutralizing ; Autoantibodies ; Immunoglobulin G ; Interferon Type I ; Interferon-alpha ; interferon omega 1
Language	English
Publishing date	2019-12-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abl4340
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies.

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Article ; Online: Autoantibodies neutralizing type I IFNs are present in

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