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

• DOI: 10.1089/jir.2023.0003
• Publication Date: 2023-05-30T14:37:50Z
• 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 Casa...; Kai Kisand
• Keywords: Interferon Lambda; type I interferons; autoantibodies; SARS-CoV-2; type III interferons; Interferon Type I; Humans; COVID-19; Interferon-alpha; Interferons; Autoantibodies

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.