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Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus
Sarthak Gupta1, Shuichiro Nakabo1, Jun Chu1
1Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda MD, 20892, USA.
Objectives:
Anti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE). Recently, an association of these autoantibodies with severe COVID-19 was reported in the general population. We assessed whether having pre-existing anti-IFNα autoantibodies was associated with COVID-19 infection in SLE patients.
Methods:
Patients with SLE who developed COVID-19 between April 1st to October 1st, 2020 were studied. Biobanked pre-COVID-19 plasma from these SLE subjects and healthy controls were tested for anti-IFNα IgG autoantibodies by ELISA. The ability of plasma anti-IFNα autoantibodies to block signal transducer and activator of transcription 1 (STAT1) phosphorylation by recombinant human IFNα in vitro was assessed by flow cytometry.
Results:
Ten SLE subjects with COVID-19 were identified. A 40% of these subjects had stable autoantibodies against IFNα for up to three years preceding COVID-19 diagnosis. A 50% of the subjects with these autoantibodies neutralized IFNα induced STAT1 phosphorylation. None of the other SLE samples blocked IFNα signaling.
Conclusions:
We noted an increased prevalence of pre-existing anti-IFNα autoantibodies in SLE patients with COVID-19 compared to the reported prevalence in lupus patients and the general population with severe COVID-19. Autoantibodies against IFNα in SLE patients may be pathogenic and patients with them maybe at-risk of developing COVID-19.
