Lower disease activity but higher risk of severe COVID-19 and herpes zoster in systemic lupus erythematosus patients with pre-existing autoantibodies neutralising IFN-α - Sorbonne Université Access content directly
Journal Articles (Data Paper) Annals of the Rheumatic Diseases Year : 2022

Lower disease activity but higher risk of severe COVID-19 and herpes zoster in systemic lupus erythematosus patients with pre-existing autoantibodies neutralising IFN-α

Pascale Ghillani-Dalbin
  • Function : Author

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.
Fichier principal
Vignette du fichier
anti IFN SLE final.pdf (2.42 Mo) Télécharger le fichier
Origin : Files produced by the author(s)
Licence : CC BY NC - Attribution - NonCommercial

Dates and versions

hal-03934607 , version 1 (02-03-2023)

Licence

Attribution - NonCommercial

Identifiers

Cite

Alexis Mathian, Paul Breillat, Karim Dorgham, Paul Bastard, Caroline Charre, et al.. Lower disease activity but higher risk of severe COVID-19 and herpes zoster in systemic lupus erythematosus patients with pre-existing autoantibodies neutralising IFN-α. Annals of the Rheumatic Diseases, 2022, 81 (12), pp.1695-1703. ⟨10.1136/ard-2022-222549⟩. ⟨hal-03934607⟩
123 View
45 Download

Altmetric

Share

Gmail Facebook X LinkedIn More