Lower disease activity but higher risk of severe COVID-19 and herpes zoster in patients with systemic lupus erythematosus with pre-existing autoantibodies neutralising IFN-α. Issue 12 (16th August 2022)

• Record Type: Journal Article
• Authors: Mathian, Alexis; Breillat, Paul; Dorgham, Karim; Bastard, Paul; Charre, Caroline; Lhote, Raphael; Quentric, Paul; Moyon, Quentin; Mariaggi, Alice-Andrée; Mouries-Martin, Suzanne; Mellot, Clara; Anna, François; Haroche, Julien; Cohen-Aubart, Fleur; Sterlin, Delphine; Zahr, Noël; Gervais, Adrian; Le Voyer, Tom; Bizien, Lucy; Amiot, Quentin; Pha, Micheline; Hié, Miguel; Chasset, Francois; Yssel, Hans; Miyara, Makoto; Charneau, Pierre; Ghillani-Dalbin, Pascale; Casanova, Jean-Laurent; Rozenberg, Flore; Amoura, Zahir; Gorochov, Guy;
• Is Part Of: Annals of the rheumatic diseases. Volume 81:Issue 12(2022)
• Page Start: 1695
• Page End: 1703
• Publication Date: 2022-08-16
• Subjects: COVID-19 -- lupus erythematosus, systemic -- cytokines -- inflammation -- autoimmunity; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard-2022-222549
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: Type-I interferons (IFNs-I) have potent antiviral effects. IFNs-I are also overproduced in patients with systemic lupus erythematosus (SLE). Autoantibodies (AAbs) neutralising IFN-α, IFN-β and/or IFN-ω subtypes are strong determinants of hypoxemic COVID-19 pneumonia, but their impact on inflammation remains unknown. Methods: We retrospectively analysed a monocentric longitudinal cohort of 609 patients with SLE. Serum AAbs against IFN-α were quantified by ELISA and functionally assessed by abolishment of Madin-Darby bovine kidney cell protection by IFN-α2 against vesicular stomatitis virus challenge. Serum-neutralising activity against IFN-α2, IFN-β and IFN-ω was also determined with a reporter luciferase activity assay. SARS-CoV-2 antibody responses were measured against wild-type spike antigen, while serum-neutralising activity was assessed against the SARS-CoV-2 historical strain and variants of concerns. Results: Neutralising and non-neutralising anti-IFN-α antibodies are present at a frequency of 3.3% and 8.4%, respectively, in individuals with SLE. AAbs neutralising IFN-α, unlike non-neutralising AAbs, are associated with reduced IFN-α serum levels and a reduced likelihood to develop active disease. However, they predispose patients to an increased risk of herpes zoster and severe COVID-19 pneumonia. Severe COVID-19 pneumonia in patients with SLE is mostly associated with combined neutralisation of different IFNs-I. Finally, anti-IFN-α AAbs do not interfere with COVID-19 vaccine humoral immunogenicity. Conclusion: The production of non-neutralising and neutralising anti-IFN-I antibodies in SLE is likely to be a consequence of SLE-associated high IFN-I serum levels, with a beneficial effect on disease activity, yet a greater viral risk. This finding reinforces the recommendations for vaccination against SARS-CoV-2 in SLE.