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

  1. Sarthak Gupta
  2. Shuichiro Nakabo
  3. Jun Chu
  4. Sarfaraz Hasni
  5. Mariana J. Kaplan

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Abstract

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 1 st to October 1 st , 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.

Key Messages

What is already known about this subject?

  • -

    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-IFNα 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 IFNα.

  • -

    SLE patients with pre-existing anti-IFNα autoantibodies had more severe COVID-19 manifestations.

    • How might this impact on clinical practice or future developments?

  • -

    Anti-IFNα 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.

    • Article activity feed

    1. ScreenIT

      SciScore for 10.1101/2020.10.29.20222000: (What is this?)

      Please note, not all rigor criteria are appropriate for all manuscripts.

      Table 1: Rigor

      Institutional Review Board Statementnot detected.
      Randomizationnot detected.
      Blindingnot detected.
      Power Analysisnot detected.
      Sex as a biological variablenot detected.

      Table 2: Resources

      Antibodies
      SentencesResources
      Patients were diagnosed with SARS-CoV-2 infection based on symptoms and a positive RT-PCR (n=6), rapid antigen (n=2) or antibody testing (n=1).
      n=6), rapid antigen (n=2)
      suggested: None
      Enzyme linked immunosorbent assay (ELISA) for anti-IFNα autoantibodies: ELISA was performed as previously reported(8).
      anti-IFNα
      suggested: None
      Functional evaluation of anti-IFNα autoantibodies: The blocking activity of anti-IFNα autoantibodies in plasma was determined by assessing phosphorylated signal transducer and activator of transcription 1 (pSTAT1) in healthy control peripheral blood mononuclear cells (PBMCs) following stimulation with rhIFNα in the presence of 10% healthy control or lupus plasma as previously described(7).
      activator of transcription 1 (pSTAT1) in healthy control peripheral blood mononuclear cells (PBMCs) following stimulation with rhIFNα in the presence of 10% healthy control or lupus plasma
      suggested: None
      Software and Algorithms
      SentencesResources
      Statistical Analysis: Data were plotted and statistical analysis performed using GraphPad Prism version 7.
      GraphPad Prism
      suggested: (GraphPad Prism, RRID:SCR_002798)

      Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

      Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

      Results from TrialIdentifier: No clinical trial numbers were referenced.

      Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

      Results from JetFighter: We did not find any issues relating to colormaps.

      Results from rtransparent:
      • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
      • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
      • No protocol registration statement was detected.

      About SciScore

      SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

    2. Version published to 10.1101/2020.10.29.20222000v1 on medRxiv