Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia

Martti Vanker; Karita Särekannu; Arnaud Fekkar; Sofie Eg Jørgensen; Liis Haljasmägi; Anne Kallaste; Kai Kisand; Margus Lember; Pärt Peterson; Madhvi Menon; Tracy Hussell; Sean Knight; James Moore-Stanley; Paul Bastard; Shen Ying Zhang; Trine H. Mogensen; Quentin Philippot; Qian Zhang; Anne Puel; Jean Laurent Casanova; Kai Kisand

doi:10.1089/jir.2023.0003

Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia

Martti Vanker, Karita Särekannu, Arnaud Fekkar, Sofie Eg Jørgensen, Liis Haljasmägi, Anne Kallaste, Kai Kisand, Margus Lember, Pärt Peterson, Madhvi Menon, Tracy Hussell, Sean Knight, James Moore-Stanley, Paul Bastard, Shen Ying Zhang, Trine H. Mogensen, Quentin Philippot, Qian Zhang, Anne Puel, Jean Laurent CasanovaKai Kisand

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

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Abstract

Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; P < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.

Originalsprog	Engelsk
Tidsskrift	Journal of Interferon & Cytokine Research
Vol/bind	43
Nummer	9
Sider (fra-til)	379-393
Antal sider	15
ISSN	1079-9907
DOI	https://doi.org/10.1089/jir.2023.0003
Status	Udgivet - 1 sep. 2023

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10.1089/jir.2023.0003Licens: CC BY

vanker-et-al-2023-autoantibodies-neutralizing-type-iii-interferons-are-uncommon-in-patients-with-severe-coronavirusForlagets udgivne version, 675 KBLicens: CC BY

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Vanker, M., Särekannu, K., Fekkar, A., Jørgensen, S. E., Haljasmägi, L., Kallaste, A., Kisand, K., Lember, M., Peterson, P., Menon, M., Hussell, T., Knight, S., Moore-Stanley, J., Bastard, P., Zhang, S. Y., Mogensen, T. H., Philippot, Q., Zhang, Q., Puel, A., ... Kisand, K. (2023). Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia. Journal of Interferon & Cytokine Research, 43(9), 379-393. https://doi.org/10.1089/jir.2023.0003

@article{35724536a5814d4ab68821ab8c345726,

title = "Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia",

abstract = "Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; P < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.",

keywords = "autoantibodies, COVID-19, type I interferons, type III interferons",

author = "Martti Vanker and Karita S{\"a}rekannu and Arnaud Fekkar and J{\o}rgensen, {Sofie Eg} and Liis Haljasm{\"a}gi and Anne Kallaste and Kai Kisand and Margus Lember and P{\"a}rt Peterson and Madhvi Menon and Tracy Hussell and Sean Knight and James Moore-Stanley and Paul Bastard and Zhang, {Shen Ying} and Mogensen, {Trine H.} and Quentin Philippot and Qian Zhang and Anne Puel and Casanova, {Jean Laurent} and Kai Kisand",

year = "2023",

month = sep,

day = "1",

doi = "10.1089/jir.2023.0003",

language = "English",

volume = "43",

pages = "379--393",

journal = "Journal of Interferon & Cytokine Research",

issn = "1079-9907",

publisher = "Mary Ann Liebert Inc.",

number = "9",

}

Vanker, M, Särekannu, K, Fekkar, A, Jørgensen, SE, Haljasmägi, L, Kallaste, A, Kisand, K, Lember, M, Peterson, P, Menon, M, Hussell, T, Knight, S, Moore-Stanley, J, Bastard, P, Zhang, SY, Mogensen, TH, Philippot, Q, Zhang, Q, Puel, A, Casanova, JL & Kisand, K 2023, 'Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia', Journal of Interferon & Cytokine Research, bind 43, nr. 9, s. 379-393. https://doi.org/10.1089/jir.2023.0003

Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia. / Vanker, Martti; Särekannu, Karita; Fekkar, Arnaud et al.
I: Journal of Interferon & Cytokine Research, Bind 43, Nr. 9, 01.09.2023, s. 379-393.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

TY - JOUR

T1 - Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia

AU - Vanker, Martti

AU - Särekannu, Karita

AU - Fekkar, Arnaud

AU - Jørgensen, Sofie Eg

AU - Haljasmägi, Liis

AU - Kallaste, Anne

AU - Kisand, Kai

AU - Lember, Margus

AU - Peterson, Pärt

AU - Menon, Madhvi

AU - Hussell, Tracy

AU - Knight, Sean

AU - Moore-Stanley, James

AU - Bastard, Paul

AU - Zhang, Shen Ying

AU - Mogensen, Trine H.

AU - Philippot, Quentin

AU - Zhang, Qian

AU - Puel, Anne

AU - Casanova, Jean Laurent

AU - Kisand, Kai

PY - 2023/9/1

Y1 - 2023/9/1

N2 - Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; P < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.

AB - Autoantibodies (AABs) neutralizing type I interferons (IFN) underlie about 15% of cases of critical coronavirus disease 2019 (COVID-19) pneumonia. The impact of autoimmunity toward type III IFNs remains unexplored. We included samples from 1,002 patients with COVID-19 (50% with severe disease) and 1,489 SARS-CoV-2-naive individuals. We studied the prevalence and neutralizing capacity of AABs toward IFNλ and IFNα. Luciferase-based immunoprecipitation method was applied using pooled IFNα (subtypes 1, 2, 8, and 21) or pooled IFNλ1-IFNλ3 as antigens, followed by reporter cell-based neutralization assay. In the SARS-CoV-2-naive cohort, IFNλ AABs were more common (8.5%) than those targeting IFNα2 (2.9%) and were related with older age. In the COVID-19 cohort the presence of autoreactivity to IFNλ did not associate with severe disease [odds ratio (OR) 0.84; 95% confidence interval (CI) 0.40-1.73], unlike to IFNα (OR 4.88; 95% CI 2.40-11.06; P < 0.001). Most IFNλ AAB-positive COVID-19 samples (67%) did not neutralize any of the 3 IFNλ subtypes. Pan-IFNλ neutralization occurred in 5 patients (0.50%), who all suffered from severe COVID-19 pneumonia, and 4 of them neutralized IFNα2 in addition to IFNλ. Overall, AABs to type III IFNs are rarely neutralizing, and do not seem to predispose to severe COVID-19 pneumonia on their own.

KW - autoantibodies

KW - COVID-19

KW - type I interferons

KW - type III interferons

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U2 - 10.1089/jir.2023.0003

DO - 10.1089/jir.2023.0003

M3 - Journal article

C2 - 37253131

AN - SCOPUS:85171808202

SN - 1079-9907

VL - 43

SP - 379

EP - 393

JO - Journal of Interferon & Cytokine Research

JF - Journal of Interferon & Cytokine Research

IS - 9

ER -

Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia

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