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 # 1 2 3 , Andrés Pizzorno # 4 , Lisa Miorin # 5 6 , Paul Bastard # 1 2 3 7 , Adrian Gervais # 2 3 , Tom Le Voyer # 2 3 , Lucy Bizien # 2 3 , Jeremy Manry 2 3 , Jérémie Rosain 2 3 , Quentin Philippot 2 3 , Kelian Goavec 2 3 , Blandine Padey 4 8 , Anastasija Cupic 5 , Emilie Laurent 4 9 , Kahina Saker 10 , Martti Vanker 11 , Karita Särekannu 11 , 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 12 13 , Marcela Ferres 12 , Nicole Le Corre 12 , Javier Sánchez-Céspedes 14 15 16 , María Balsera-Manzanero 14 15 16 , Jordi Carratala 14 17 18 , Pilar Retamar-Gentil 14 16 19 , Gabriela Abelenda-Alonso 17 20 , Adoración Valiente 14 15 19 , Pierre Tiberghien 21 , Marie Zins 22 , Stéphanie Debette 23 , Isabelle Meyts 24 , Filomeen Haerynck 25 , Riccardo Castagnoli 26 , Luigi D Notarangelo 26 , Luis I Gonzalez-Granado 27 , Nerea Dominguez-Pinilla 28 , Evangelos Andreakos 29 , Vasiliki Triantafyllia 29 , Carlos Rodríguez-Gallego 30 31 , Jordi Solé-Violán 31 32 33 , José Juan Ruiz-Hernandez 34 , Felipe Rodríguez de Castro 35 36 , José Ferreres 37 38 , Marisa Briones 39 , Joost Wauters 40 , Lore Vanderbeke 40 , Simon Feys 40 , Chen-Yen Kuo 41 42 , Wei-Te Lei 41 43 , Cheng-Lung Ku 41 44 45 , Galit Tal 46 47 , Amos Etzioni 46 , Suhair Hanna 46 , Thomas Fournet 48 , Jean-Sebastien Casalegno 49 , Gregory Queromes 4 , Laurent Argaud 50 , Etienne Javouhey 51 , Manuel Rosa-Calatrava 4 9 , Elisa Cordero 14 15 16 52 , Teresa Aydillo 5 6 , Rafael A Medina 5 12 , Kai Kisand # 11 , Anne Puel # 1 2 3 , Emmanuelle Jouanguy # 1 2 3 , Laurent Abel # 1 2 3 , Aurélie Cobat # 1 2 3 , Sophie Trouillet-Assant # 4 10 , Adolfo García-Sastre # 5 6 53 54 55 , Jean-Laurent Casanova # 1 2 3 7 56
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.