Autoantibodies against type I IFNs in patients with critical influenza pneumonia

Qian Zhang; Andrés Pizzorno; Lisa Miorin; Paul Bastard; Adrian Gervais; Tom Le Voyer; Lucy Bizien; Jeremy Manry; Jérémie Rosain; Quentin Philippot; Kelian Goavec; Blandine Padey; Anastasija Cupic; Emilie Laurent; Kahina Saker; Martti Vanker; Karita Särekannu; Tamara García-Salum; Marcela Ferres; Nicole Le Corre; Javier Sánchez-Céspedes; María Balsera-Manzanero; Jordi Carratala; Pilar Retamar-Gentil; Gabriela Abelenda-Alonso; Adoración Valiente; Pierre Tiberghien; Marie Zins; Stéphanie Debette; Isabelle Meyts; Filomeen Haerynck; Riccardo Castagnoli; Luigi D. Notarangelo; Luis I. Gonzalez-Granado; Nerea Dominguez-Pinilla; Evangelos Andreakos; Vasiliki Triantafyllia; Carlos Rodríguez-Gallego; Jordi Solé-Violán; José Juan Ruiz-Hernandez; Felipe Rodríguez de Castro; José Ferreres; Marisa Briones; Joost Wauters; Lore Vanderbeke; Simon Feys; Chen Yen Kuo; Wei Te Lei; Cheng Lung Ku; Galit Tal; Amos Etzioni; Suhair Hanna; Thomas Fournet; Jean Sebastien Casalegno; Gregory Queromes; Laurent Argaud; Etienne Javouhey; Manuel Rosa-Calatrava; Elisa Cordero; Teresa Aydillo; Rafael A. Medina; Kai Kisand; Anne Puel; Emmanuelle Jouanguy; Laurent Abel; Aurélie Cobat; Sophie Trouillet-Assant; Adolfo García-Sastre; Jean Laurent Casanova

doi:10.1084/jem.20220514

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

Qian Zhang, Andrés Pizzorno, Lisa Miorin, Paul Bastard, Adrian Gervais, Tom Le Voyer, Lucy Bizien, Jeremy Manry, Jérémie Rosain, Quentin Philippot, Kelian Goavec, Blandine Padey, Anastasija Cupic, Emilie Laurent, Kahina Saker, Martti Vanker, Karita Särekannu, Tamara García-Salum, Marcela Ferres, Nicole Le CorreJavier Sánchez-Céspedes, María Balsera-Manzanero, Jordi Carratala, Pilar Retamar-Gentil, Gabriela Abelenda-Alonso, Adoración Valiente, Pierre Tiberghien, Marie Zins, Stéphanie Debette, Isabelle Meyts, Filomeen Haerynck, Riccardo Castagnoli, Luigi D. Notarangelo, Luis I. Gonzalez-Granado, Nerea Dominguez-Pinilla, Evangelos Andreakos, Vasiliki Triantafyllia, Carlos Rodríguez-Gallego, Jordi Solé-Violán, José Juan Ruiz-Hernandez, Felipe Rodríguez de Castro, José Ferreres, Marisa Briones, Joost Wauters, Lore Vanderbeke, Simon Feys, Chen Yen Kuo, Wei Te Lei, Cheng Lung Ku, Galit Tal, Amos Etzioni, Suhair Hanna, Thomas Fournet, Jean Sebastien Casalegno, Gregory Queromes, Laurent Argaud, Etienne Javouhey, Manuel Rosa-Calatrava, Elisa Cordero, Teresa Aydillo, Rafael A. Medina, Kai Kisand, Anne Puel, Emmanuelle Jouanguy, Laurent Abel, Aurélie Cobat, Sophie Trouillet-Assant, Adolfo García-Sastre, Jean Laurent Casanova

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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.

Original language	English
Article number	e20220514
Journal	Journal of Experimental Medicine
Volume	219
Issue number	11
DOIs	https://doi.org/10.1084/jem.20220514
State	Published - 7 Nov 2022

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10.1084/jem.20220514

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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., ... Casanova, J. L. (2022). Autoantibodies against type I IFNs in patients with critical influenza pneumonia. Journal of Experimental Medicine, 219(11), Article e20220514. https://doi.org/10.1084/jem.20220514

@article{8ba6159be5a84b97910d053dca3116aa,

title = "Autoantibodies against type I IFNs in patients with critical influenza pneumonia",

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{\textquoteright} 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.",

author = "Qian Zhang and Andr{\'e}s Pizzorno and Lisa Miorin and Paul Bastard and Adrian Gervais and {Le Voyer}, Tom and Lucy Bizien and Jeremy Manry and J{\'e}r{\'e}mie Rosain and Quentin Philippot and Kelian Goavec and Blandine Padey and Anastasija Cupic and Emilie Laurent and Kahina Saker and Martti Vanker and Karita S{\"a}rekannu and Tamara Garc{\'i}a-Salum and Marcela Ferres and Corre, {Nicole Le} and Javier S{\'a}nchez-C{\'e}spedes and Mar{\'i}a Balsera-Manzanero and Jordi Carratala and Pilar Retamar-Gentil and Gabriela Abelenda-Alonso and Adoraci{\'o}n Valiente and Pierre Tiberghien and Marie Zins and St{\'e}phanie Debette and Isabelle Meyts and Filomeen Haerynck and Riccardo Castagnoli and Notarangelo, {Luigi D.} and Gonzalez-Granado, {Luis I.} and Nerea Dominguez-Pinilla and Evangelos Andreakos and Vasiliki Triantafyllia and Carlos Rodr{\'i}guez-Gallego and Jordi Sol{\'e}-Viol{\'a}n and Ruiz-Hernandez, {Jos{\'e} Juan} and {de Castro}, {Felipe Rodr{\'i}guez} and Jos{\'e} Ferreres and Marisa Briones and Joost Wauters and Lore Vanderbeke and Simon Feys and Kuo, {Chen Yen} and Lei, {Wei Te} and Ku, {Cheng Lung} and Galit Tal and Amos Etzioni and Suhair Hanna and Thomas Fournet and Casalegno, {Jean Sebastien} and Gregory Queromes and Laurent Argaud and Etienne Javouhey and Manuel Rosa-Calatrava and Elisa Cordero and Teresa Aydillo and Medina, {Rafael A.} and Kai Kisand and Anne Puel and Emmanuelle Jouanguy and Laurent Abel and Aur{\'e}lie Cobat and Sophie Trouillet-Assant and Adolfo Garc{\'i}a-Sastre and Casanova, {Jean Laurent}",

note = "Publisher Copyright: {\textcopyright} 2022 Zhang et al.",

year = "2022",

month = nov,

day = "7",

doi = "10.1084/jem.20220514",

language = "English",

volume = "219",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

publisher = "Rockefeller University Press",

number = "11",

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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, Corre, NL, 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, de Castro, FR, 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 & Casanova, JL 2022, 'Autoantibodies against type I IFNs in patients with critical influenza pneumonia', Journal of Experimental Medicine, vol. 219, no. 11, e20220514. https://doi.org/10.1084/jem.20220514

TY - JOUR

T1 - Autoantibodies against type I IFNs in patients with critical influenza pneumonia

AU - Zhang, Qian

AU - Pizzorno, Andrés

AU - Miorin, Lisa

AU - Bastard, Paul

AU - Gervais, Adrian

AU - Le Voyer, Tom

AU - Bizien, Lucy

AU - Manry, Jeremy

AU - Rosain, Jérémie

AU - Philippot, Quentin

AU - Goavec, Kelian

AU - Padey, Blandine

AU - Cupic, Anastasija

AU - Laurent, Emilie

AU - Saker, Kahina

AU - Vanker, Martti

AU - Särekannu, Karita

AU - García-Salum, Tamara

AU - Ferres, Marcela

AU - Corre, Nicole Le

AU - Sánchez-Céspedes, Javier

AU - Balsera-Manzanero, María

AU - Carratala, Jordi

AU - Retamar-Gentil, Pilar

AU - Abelenda-Alonso, Gabriela

AU - Valiente, Adoración

AU - Tiberghien, Pierre

AU - Zins, Marie

AU - Debette, Stéphanie

AU - Meyts, Isabelle

AU - Haerynck, Filomeen

AU - Castagnoli, Riccardo

AU - Notarangelo, Luigi D.

AU - Gonzalez-Granado, Luis I.

AU - Dominguez-Pinilla, Nerea

AU - Andreakos, Evangelos

AU - Triantafyllia, Vasiliki

AU - Rodríguez-Gallego, Carlos

AU - Solé-Violán, Jordi

AU - Ruiz-Hernandez, José Juan

AU - de Castro, Felipe Rodríguez

AU - Ferreres, José

AU - Briones, Marisa

AU - Wauters, Joost

AU - Vanderbeke, Lore

AU - Feys, Simon

AU - Kuo, Chen Yen

AU - Lei, Wei Te

AU - Ku, Cheng Lung

AU - Tal, Galit

AU - Etzioni, Amos

AU - Hanna, Suhair

AU - Fournet, Thomas

AU - Casalegno, Jean Sebastien

AU - Queromes, Gregory

AU - Argaud, Laurent

AU - Javouhey, Etienne

AU - Rosa-Calatrava, Manuel

AU - Cordero, Elisa

AU - Aydillo, Teresa

AU - Medina, Rafael A.

AU - Kisand, Kai

AU - Puel, Anne

AU - Jouanguy, Emmanuelle

AU - Abel, Laurent

AU - Cobat, Aurélie

AU - Trouillet-Assant, Sophie

AU - García-Sastre, Adolfo

AU - Casanova, Jean Laurent

PY - 2022/11/7

Y1 - 2022/11/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85136198376&partnerID=8YFLogxK

U2 - 10.1084/jem.20220514

DO - 10.1084/jem.20220514

M3 - Article

C2 - 36112363

AN - SCOPUS:85136198376

SN - 0022-1007

VL - 219

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

IS - 11

M1 - e20220514

ER -

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

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