tetano
Editor, Senior Moderator
J Exp Med
. 2026 Mar 2;223(3):e20251962.
doi: 10.1084/jem.20251962. Epub 2025 Dec 5. Autoantibodies neutralizing type I IFNs in a fatal case of H5N1 avian influenza
Qian Zhang[SUP] 1 2 3 [/SUP], Taylor S Conrad[SUP] #[/SUP][SUP] 4 5 [/SUP], Marcela Moncada-Velez[SUP] #[/SUP][SUP] 1 [/SUP], Kaijun Jiang[SUP] #[/SUP][SUP] 6 7 [/SUP], Anastasija Cupic[SUP] #[/SUP][SUP] 6 7 [/SUP], Jonathan Eaton[SUP] 4 [/SUP], Kimberley Hutchinson[SUP] 5 [/SUP], Adrian Gervais[SUP] 2 3 [/SUP], Ruyue Chen[SUP] 1 8 [/SUP], Anne Puel[SUP] 1 2 3 [/SUP], Paul Bastard[SUP] 1 2 3 9 [/SUP], Aurelie Cobat[SUP] 1 2 3 [/SUP], Theresa Sokol[SUP] 10 [/SUP], Ryan A Langlois[SUP] 11 [/SUP], Lisa Miorin[SUP] 6 12 [/SUP], Adolfo García-Sastre[SUP] #[/SUP][SUP] 6 13 14 15 16 [/SUP], John A Vanchiere[SUP] #[/SUP][SUP] 17 [/SUP], Jean-Laurent Casanova[SUP] 1 2 3 9 18 [/SUP]
Affiliations
Avian influenza A virus (IAV) H5N1 is an emerging threat of human pandemic. We describe a 71-year-old man who died of H5N1 pneumonia in Louisiana and whose blood contained autoantibodies neutralizing type I IFNs (AAN-I-IFNs), including the 12 IFN-α subtypes (1-10 ng/ml) and IFN-ω (100 pg/ml). Causality between these AAN-I-IFN and lethal outcome of avian influenza in this patient is based on (1) our previous report that AA-I-IFN underlie about 5% of cases of critical pneumonia triggered by seasonal influenza viruses in three cohorts, (2) the rarity of this combination of AAN-I-FNs in individuals over 70 years old (<1%), and (3) the rarity of lethal avian influenza among infected individuals (<1%). AAN-I-IFNs underlie a growing number of severe viral diseases, from arboviral encephalitis to viral pneumonia, particularly in the elderly. This case suggests they can also underlie life-threatening avian H5N1 influenza. The presence of AAN-I-IFN may facilitate infection, replication, and adaptation of zoonotic IAVs to humans and, therefore, human-to-human transmission.
. 2026 Mar 2;223(3):e20251962.
doi: 10.1084/jem.20251962. Epub 2025 Dec 5. Autoantibodies neutralizing type I IFNs in a fatal case of H5N1 avian influenza
Qian Zhang[SUP] 1 2 3 [/SUP], Taylor S Conrad[SUP] #[/SUP][SUP] 4 5 [/SUP], Marcela Moncada-Velez[SUP] #[/SUP][SUP] 1 [/SUP], Kaijun Jiang[SUP] #[/SUP][SUP] 6 7 [/SUP], Anastasija Cupic[SUP] #[/SUP][SUP] 6 7 [/SUP], Jonathan Eaton[SUP] 4 [/SUP], Kimberley Hutchinson[SUP] 5 [/SUP], Adrian Gervais[SUP] 2 3 [/SUP], Ruyue Chen[SUP] 1 8 [/SUP], Anne Puel[SUP] 1 2 3 [/SUP], Paul Bastard[SUP] 1 2 3 9 [/SUP], Aurelie Cobat[SUP] 1 2 3 [/SUP], Theresa Sokol[SUP] 10 [/SUP], Ryan A Langlois[SUP] 11 [/SUP], Lisa Miorin[SUP] 6 12 [/SUP], Adolfo García-Sastre[SUP] #[/SUP][SUP] 6 13 14 15 16 [/SUP], John A Vanchiere[SUP] #[/SUP][SUP] 17 [/SUP], Jean-Laurent Casanova[SUP] 1 2 3 9 18 [/SUP]
Affiliations
- PMID: 41348320
- DOI: 10.1084/jem.20251962
Avian influenza A virus (IAV) H5N1 is an emerging threat of human pandemic. We describe a 71-year-old man who died of H5N1 pneumonia in Louisiana and whose blood contained autoantibodies neutralizing type I IFNs (AAN-I-IFNs), including the 12 IFN-α subtypes (1-10 ng/ml) and IFN-ω (100 pg/ml). Causality between these AAN-I-IFN and lethal outcome of avian influenza in this patient is based on (1) our previous report that AA-I-IFN underlie about 5% of cases of critical pneumonia triggered by seasonal influenza viruses in three cohorts, (2) the rarity of this combination of AAN-I-FNs in individuals over 70 years old (<1%), and (3) the rarity of lethal avian influenza among infected individuals (<1%). AAN-I-IFNs underlie a growing number of severe viral diseases, from arboviral encephalitis to viral pneumonia, particularly in the elderly. This case suggests they can also underlie life-threatening avian H5N1 influenza. The presence of AAN-I-IFN may facilitate infection, replication, and adaptation of zoonotic IAVs to humans and, therefore, human-to-human transmission.