Title |
Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia
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Published in |
Journal of Interferon & Cytokine Research, May 2023
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DOI | 10.1089/jir.2023.0003 |
Pubmed ID | |
Authors |
Martti Vanker, Karita Särekannu, Arnaud Fekkar, Sofie Eg Jørgensen, Liis Haljasmägi, Anne Kallaste, Kalle 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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 3 | 12% |
France | 2 | 8% |
India | 2 | 8% |
Guinea | 1 | 4% |
Sweden | 1 | 4% |
Canada | 1 | 4% |
Ireland | 1 | 4% |
Australia | 1 | 4% |
Netherlands | 1 | 4% |
Other | 2 | 8% |
Unknown | 10 | 40% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 16 | 64% |
Scientists | 6 | 24% |
Practitioners (doctors, other healthcare professionals) | 3 | 12% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 8 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 2 | 25% |
Professor | 1 | 13% |
Other | 1 | 13% |
Student > Master | 1 | 13% |
Unknown | 3 | 38% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 2 | 25% |
Biochemistry, Genetics and Molecular Biology | 1 | 13% |
Medicine and Dentistry | 1 | 13% |
Unknown | 4 | 50% |