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Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus

By Sarthak Gupta, Shuichiro Nakabo, Jun Chu, Sarfaraz Hasni, Mariana J. Kaplan

Posted 03 Nov 2020
medRxiv DOI: 10.1101/2020.10.29.20222000

ObjectivesAnti-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-IFN autoantibodies was associated with COVID-19 infection in SLE patients. MethodsPatients 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-IFN IgG autoantibodies by ELISA. The ability of plasma anti-IFN autoantibodies to block signal transducer and activator of transcription 1 (STAT1) phosphorylation by recombinant human IFN in vitro was assessed by flow cytometry. ResultsTen SLE subjects with COVID-19 were identified. A 40% of these subjects had stable autoantibodies against IFN for up to three years preceding COVID-19 diagnosis. A 50% of the subjects with these autoantibodies neutralized IFN induced STAT1 phosphorylation.None of the other SLE samples blocked IFN signaling. ConclusionsWe noted an increased prevalence of pre-existing anti-IFN 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 IFN in SLE patients may be pathogenic and patients with them maybe at-risk of developing COVID-19. Key MessagesO_ST_ABSWhat is already known about this subject?C_ST_ABS- Anti-type I interferon (IFN) autoantibodies have been reported in patients with systemic lupus erythematosus (SLE) and have recently been associated with severe COVID-19 in the general population. What does this study add?- SLE subjects with COVID-19 had an increased prevalence of pre-existing anti-IFN autoantibodies compared to the reported prevalence in lupus patients and the general population with severe COVID-19. - Plasma from 50% of subjects with these autoantibodies were able to block in vitro activity of IFN. - SLE patients with pre-existing anti-IFN autoantibodies had more severe COVID-19 manifestations. How might this impact on clinical practice or future developments?- Anti-IFN autoantibodies may be pathogenic and could prove to be a helpful prognostic marker to predict which SLE patient may develop COVID-19 and inform preventive measures and management of this subset of patients.

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