TY - JOUR
T1 - Autoantibodies against type I IFNs in patients with critical influenza pneumonia
AU - COVID Human Genetic Effort
AU - Etablissement Français du Sang Study group
AU - CONSTANCES cohort
AU - 3C-Dijon Study
AU - Cerba HealthCare Group
AU - Lyon Antigrippe Working Group
AU - REIPI INF Working Group
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 - Le Corre, Nicole
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 - Juan Ruiz-Hernandez, José
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 - Halwani, Rabih
AU - Uddin, Mohammed J.
N1 - Publisher Copyright:
© 2022 Zhang et al.
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 - https://www.scopus.com/pages/publications/85136198376
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 -
SDG 3 Good Health and Well-being