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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; Abel, Laurent; Aiuti, Alessandro; Al-Muhsen, Saleh; Al-Mulla, Fahd; Anderson, Mark S.; Andreakos, Evangelos; Arias, Andrés A.; [...]

Autoantibodies against type I IFNs in patients with critical influenza pneumonia

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  • Medientyp: E-Artikel
  • Titel: Autoantibodies against type I IFNs in patients with critical influenza pneumonia
  • Beteiligte: 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; Abel, Laurent; Aiuti, Alessandro; Al-Muhsen, Saleh; Al-Mulla, Fahd; Anderson, Mark S.; Andreakos, Evangelos; Arias, Andrés A.; [...]
  • Erschienen: Rockefeller University Press, 2022
  • Erschienen in: Journal of Experimental Medicine
  • Sprache: Englisch
  • DOI: 10.1084/jem.20220514
  • ISSN: 0022-1007; 1540-9538
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:p>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 &amp;lt;70 yr of age (5.7 vs. 1.1%, P = 2.2 × 10−5), but not &amp;gt;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 &amp;lt;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 &amp;lt;70 yr old.</jats:p>
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