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 Casanova

Kai Kisand

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

15 Citations (Scopus)

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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.

Original language	English
Journal	Journal of Interferon & Cytokine Research
Volume	43
Issue	9
Pages (from-to)	379-393
Number of pages	15
ISSN	1079-9907
DOIs	https://doi.org/10.1089/jir.2023.0003
Publication status	Published - 1 Sept 2023

Keywords

autoantibodies
COVID-19
type I interferons
type III interferons

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vanker-et-al-2023-autoantibodies-neutralizing-type-iii-interferons-are-uncommon-in-patients-with-severe-coronavirusFinal published version, 675 KBLicence: 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, vol. 43, no. 9, pp. 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.
In: Journal of Interferon & Cytokine Research, Vol. 43, No. 9, 01.09.2023, p. 379-393.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › 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

UR - https://www.scopus.com/pages/publications/85171808202

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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