tetano
Editor, Senior Moderator
J Exp Med
. 2022 Nov 7;219(11):e20220514.
doi: 10.1084/jem.20220514. Epub 2022 Sep 16.
Autoantibodies against type I IFNs in patients with critical influenza pneumonia
Qian Zhang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Andrés Pizzorno[SUP] #[/SUP][SUP] 4 [/SUP], Lisa Miorin[SUP] #[/SUP][SUP] 5 6 [/SUP], Paul Bastard[SUP] #[/SUP][SUP] 1 2 3 7 [/SUP], Adrian Gervais[SUP] #[/SUP][SUP] 2 3 [/SUP], Tom Le Voyer[SUP] #[/SUP][SUP] 2 3 [/SUP], Lucy Bizien[SUP] #[/SUP][SUP] 2 3 [/SUP], Jeremy Manry[SUP] 2 3 [/SUP], Jérémie Rosain[SUP] 2 3 [/SUP], Quentin Philippot[SUP] 2 3 [/SUP], Kelian Goavec[SUP] 2 3 [/SUP], Blandine Padey[SUP] 4 8 [/SUP], Anastasija Cupic[SUP] 5 [/SUP], Emilie Laurent[SUP] 4 9 [/SUP], Kahina Saker[SUP] 10 [/SUP], Martti Vanker[SUP] 11 [/SUP], Karita Särekannu[SUP] 11 [/SUP], COVID Human Genetic Effort; Etablissement Français du Sang Study Group; Constances Cohort; 3C-Dijon Study; Cerba HealthCare Group; Lyon Antigrippe Working Group; REIPI INF Working Group; Tamara García-Salum[SUP] 12 13 [/SUP], Marcela Ferres[SUP] 12 [/SUP], Nicole Le Corre[SUP] 12 [/SUP], Javier Sánchez-Céspedes[SUP] 14 15 16 [/SUP], María Balsera-Manzanero[SUP] 14 15 16 [/SUP], Jordi Carratala[SUP] 14 17 18 [/SUP], Pilar Retamar-Gentil[SUP] 14 16 19 [/SUP], Gabriela Abelenda-Alonso[SUP] 17 20 [/SUP], Adoración Valiente[SUP] 14 15 19 [/SUP], Pierre Tiberghien[SUP] 21 [/SUP], Marie Zins[SUP] 22 [/SUP], Stéphanie Debette[SUP] 23 [/SUP], Isabelle Meyts[SUP] 24 [/SUP], Filomeen Haerynck[SUP] 25 [/SUP], Riccardo Castagnoli[SUP] 26 [/SUP], Luigi D Notarangelo[SUP] 26 [/SUP], Luis I Gonzalez-Granado[SUP] 27 [/SUP], Nerea Dominguez-Pinilla[SUP] 28 [/SUP], Evangelos Andreakos[SUP] 29 [/SUP], Vasiliki Triantafyllia[SUP] 29 [/SUP], Carlos Rodríguez-Gallego[SUP] 30 31 [/SUP], Jordi Solé-Violán[SUP] 31 32 33 [/SUP], José Juan Ruiz-Hernandez[SUP] 34 [/SUP], Felipe Rodríguez de Castro[SUP] 35 36 [/SUP], José Ferreres[SUP] 37 38 [/SUP], Marisa Briones[SUP] 39 [/SUP], Joost Wauters[SUP] 40 [/SUP], Lore Vanderbeke[SUP] 40 [/SUP], Simon Feys[SUP] 40 [/SUP], Chen-Yen Kuo[SUP] 41 42 [/SUP], Wei-Te Lei[SUP] 41 43 [/SUP], Cheng-Lung Ku[SUP] 41 44 45 [/SUP], Galit Tal[SUP] 46 47 [/SUP], Amos Etzioni[SUP] 46 [/SUP], Suhair Hanna[SUP] 46 [/SUP], Thomas Fournet[SUP] 48 [/SUP], Jean-Sebastien Casalegno[SUP] 49 [/SUP], Gregory Queromes[SUP] 4 [/SUP], Laurent Argaud[SUP] 50 [/SUP], Etienne Javouhey[SUP] 51 [/SUP], Manuel Rosa-Calatrava[SUP] 4 9 [/SUP], Elisa Cordero[SUP] 14 15 16 52 [/SUP], Teresa Aydillo[SUP] 5 6 [/SUP], Rafael A Medina[SUP] 5 12 [/SUP], Kai Kisand[SUP] #[/SUP][SUP] 11 [/SUP], Anne Puel[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Emmanuelle Jouanguy[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Laurent Abel[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Aurélie Cobat[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Sophie Trouillet-Assant[SUP] #[/SUP][SUP] 4 10 [/SUP], Adolfo García-Sastre[SUP] #[/SUP][SUP] 5 6 53 54 55 [/SUP], Jean-Laurent Casanova[SUP] #[/SUP][SUP] 1 2 3 7 56 [/SUP]
Collaborators, Affiliations
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.
. 2022 Nov 7;219(11):e20220514.
doi: 10.1084/jem.20220514. Epub 2022 Sep 16.
Autoantibodies against type I IFNs in patients with critical influenza pneumonia
Qian Zhang[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Andrés Pizzorno[SUP] #[/SUP][SUP] 4 [/SUP], Lisa Miorin[SUP] #[/SUP][SUP] 5 6 [/SUP], Paul Bastard[SUP] #[/SUP][SUP] 1 2 3 7 [/SUP], Adrian Gervais[SUP] #[/SUP][SUP] 2 3 [/SUP], Tom Le Voyer[SUP] #[/SUP][SUP] 2 3 [/SUP], Lucy Bizien[SUP] #[/SUP][SUP] 2 3 [/SUP], Jeremy Manry[SUP] 2 3 [/SUP], Jérémie Rosain[SUP] 2 3 [/SUP], Quentin Philippot[SUP] 2 3 [/SUP], Kelian Goavec[SUP] 2 3 [/SUP], Blandine Padey[SUP] 4 8 [/SUP], Anastasija Cupic[SUP] 5 [/SUP], Emilie Laurent[SUP] 4 9 [/SUP], Kahina Saker[SUP] 10 [/SUP], Martti Vanker[SUP] 11 [/SUP], Karita Särekannu[SUP] 11 [/SUP], COVID Human Genetic Effort; Etablissement Français du Sang Study Group; Constances Cohort; 3C-Dijon Study; Cerba HealthCare Group; Lyon Antigrippe Working Group; REIPI INF Working Group; Tamara García-Salum[SUP] 12 13 [/SUP], Marcela Ferres[SUP] 12 [/SUP], Nicole Le Corre[SUP] 12 [/SUP], Javier Sánchez-Céspedes[SUP] 14 15 16 [/SUP], María Balsera-Manzanero[SUP] 14 15 16 [/SUP], Jordi Carratala[SUP] 14 17 18 [/SUP], Pilar Retamar-Gentil[SUP] 14 16 19 [/SUP], Gabriela Abelenda-Alonso[SUP] 17 20 [/SUP], Adoración Valiente[SUP] 14 15 19 [/SUP], Pierre Tiberghien[SUP] 21 [/SUP], Marie Zins[SUP] 22 [/SUP], Stéphanie Debette[SUP] 23 [/SUP], Isabelle Meyts[SUP] 24 [/SUP], Filomeen Haerynck[SUP] 25 [/SUP], Riccardo Castagnoli[SUP] 26 [/SUP], Luigi D Notarangelo[SUP] 26 [/SUP], Luis I Gonzalez-Granado[SUP] 27 [/SUP], Nerea Dominguez-Pinilla[SUP] 28 [/SUP], Evangelos Andreakos[SUP] 29 [/SUP], Vasiliki Triantafyllia[SUP] 29 [/SUP], Carlos Rodríguez-Gallego[SUP] 30 31 [/SUP], Jordi Solé-Violán[SUP] 31 32 33 [/SUP], José Juan Ruiz-Hernandez[SUP] 34 [/SUP], Felipe Rodríguez de Castro[SUP] 35 36 [/SUP], José Ferreres[SUP] 37 38 [/SUP], Marisa Briones[SUP] 39 [/SUP], Joost Wauters[SUP] 40 [/SUP], Lore Vanderbeke[SUP] 40 [/SUP], Simon Feys[SUP] 40 [/SUP], Chen-Yen Kuo[SUP] 41 42 [/SUP], Wei-Te Lei[SUP] 41 43 [/SUP], Cheng-Lung Ku[SUP] 41 44 45 [/SUP], Galit Tal[SUP] 46 47 [/SUP], Amos Etzioni[SUP] 46 [/SUP], Suhair Hanna[SUP] 46 [/SUP], Thomas Fournet[SUP] 48 [/SUP], Jean-Sebastien Casalegno[SUP] 49 [/SUP], Gregory Queromes[SUP] 4 [/SUP], Laurent Argaud[SUP] 50 [/SUP], Etienne Javouhey[SUP] 51 [/SUP], Manuel Rosa-Calatrava[SUP] 4 9 [/SUP], Elisa Cordero[SUP] 14 15 16 52 [/SUP], Teresa Aydillo[SUP] 5 6 [/SUP], Rafael A Medina[SUP] 5 12 [/SUP], Kai Kisand[SUP] #[/SUP][SUP] 11 [/SUP], Anne Puel[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Emmanuelle Jouanguy[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Laurent Abel[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Aurélie Cobat[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Sophie Trouillet-Assant[SUP] #[/SUP][SUP] 4 10 [/SUP], Adolfo García-Sastre[SUP] #[/SUP][SUP] 5 6 53 54 55 [/SUP], Jean-Laurent Casanova[SUP] #[/SUP][SUP] 1 2 3 7 56 [/SUP]
Collaborators, Affiliations
- PMID: 36112363
- DOI: 10.1084/jem.20220514
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.