tetano
Editor, Senior Moderator
Sci Transl Med
. 2024 Nov 6;16(772):eadq1789.
doi: 10.1126/scitranslmed.adq1789. Epub 2024 Nov 6. Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19
Benjamin R Babcock[SUP] 1 [/SUP], Astrid Kosters[SUP] 1 [/SUP], Devon J Eddins[SUP] 1 [/SUP], Maria Sophia Baluyot Donaire[SUP] 2 [/SUP], Sannidhi Sarvadhavabhatla[SUP] 2 [/SUP], Vivian Pae[SUP] 2 [/SUP], Fiona Beltran[SUP] 2 [/SUP], Victoria W Murray[SUP] 2 [/SUP], Gurjot Gill[SUP] 2 [/SUP], Guorui Xie[SUP] 3 4 [/SUP], Brian S Dobosh[SUP] 5 [/SUP], Vincent D Giacalone[SUP] 5 [/SUP], Rabindra M Tirouvanziam[SUP] 5 [/SUP], Richard P Ramonell[SUP] 6 [/SUP], Scott A Jenks[SUP] 1 [/SUP], Ignacio Sanz[SUP] 1 [/SUP], F Eun-Hyung Lee[SUP] 6 [/SUP], Nadia R Roan[SUP] 3 4 [/SUP], Sulggi A Lee[SUP] 2 [/SUP], Eliver E B Ghosn[SUP] 1 7 [/SUP]
Affiliations
Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19. We found that nasal IgA1 anti-IFN-α autoantibodies were induced after infection onset in more than 70% of mild and moderate COVID-19 cases and were associated with robust anti-SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti-IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti-IFN-α response. In contrast, systemic IgG1 anti-IFN-α autoantibodies appeared later and were detected only in a subset of patients with elevated systemic inflammation and worsening symptoms. These data reveal a protective role for nasal anti-IFN-α in the immunopathology of COVID-19 and suggest that anti-IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa.
. 2024 Nov 6;16(772):eadq1789.
doi: 10.1126/scitranslmed.adq1789. Epub 2024 Nov 6. Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19
Benjamin R Babcock[SUP] 1 [/SUP], Astrid Kosters[SUP] 1 [/SUP], Devon J Eddins[SUP] 1 [/SUP], Maria Sophia Baluyot Donaire[SUP] 2 [/SUP], Sannidhi Sarvadhavabhatla[SUP] 2 [/SUP], Vivian Pae[SUP] 2 [/SUP], Fiona Beltran[SUP] 2 [/SUP], Victoria W Murray[SUP] 2 [/SUP], Gurjot Gill[SUP] 2 [/SUP], Guorui Xie[SUP] 3 4 [/SUP], Brian S Dobosh[SUP] 5 [/SUP], Vincent D Giacalone[SUP] 5 [/SUP], Rabindra M Tirouvanziam[SUP] 5 [/SUP], Richard P Ramonell[SUP] 6 [/SUP], Scott A Jenks[SUP] 1 [/SUP], Ignacio Sanz[SUP] 1 [/SUP], F Eun-Hyung Lee[SUP] 6 [/SUP], Nadia R Roan[SUP] 3 4 [/SUP], Sulggi A Lee[SUP] 2 [/SUP], Eliver E B Ghosn[SUP] 1 7 [/SUP]
Affiliations
- PMID: 39504354
- DOI: 10.1126/scitranslmed.adq1789
Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19. We found that nasal IgA1 anti-IFN-α autoantibodies were induced after infection onset in more than 70% of mild and moderate COVID-19 cases and were associated with robust anti-SARS-CoV-2 immunity, fewer symptoms, and efficient recovery. Nasal anti-IFN-α autoantibodies followed the peak of host IFN-α production and waned with disease recovery, revealing a regulated balance between IFN-α and anti-IFN-α response. In contrast, systemic IgG1 anti-IFN-α autoantibodies appeared later and were detected only in a subset of patients with elevated systemic inflammation and worsening symptoms. These data reveal a protective role for nasal anti-IFN-α in the immunopathology of COVID-19 and suggest that anti-IFN-α autoantibodies may serve a homeostatic function to regulate host IFN-α after viral infection in the respiratory mucosa.