B cells, BAFF and interferons in MIS-C

  1. Adam Klocperk
  2. Marketa Bloomfield
  3. Zuzana Parackova
  4. Ludovic Aillot
  5. Jiri Fremuth
  6. Lumir Sasek
  7. Jan David
  8. Filip Fencl
  9. Aneta Skotnicova
  10. Katerina Rejlova
  11. Martin Magner
  12. Ondrej Hrusak
  13. Anna Sediva

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Abstract

Multisystem Inflammatory Syndrome in Children associated with COVID-19 (MIS-C) is a late complication of pediatric COVID-19, which follows weeks after original SARS-CoV-2 infection, regardless of its severity. It is characterized by hyperinflammation, neutrophilia, lymphopenia and activation of T cells with elevated IFN-γ. Observing production of autoantibodies and parallels with systemic autoimmune disorders, such as systemic lupus erythematodes (SLE), we explored B cell phenotype and serum levels of type I, II and III interferons, as well as the cytokines BAFF and APRIL in a cohort of MIS-C patients and healthy children after COVID-19.

We documented a significant elevation of IFN-γ, but not IFN-α and IFN-λ in MIS-C patients. BAFF was elevated in MIS-C patient sera and accompanied by decreased BAFFR expression on all B cell subtypes. The proportion of plasmablasts was significantly lower in patients compared to healthy post-COVID children. We noted the presence of ENA Ro60 autoantibodies in 4/35 tested MIS-C patients.

Our work shows the involvement of humoral immunity in MIS-C and hints at parallels with the pathophysiology of SLE, with autoreactive B cells driven towards autoantibody production by elevated BAFF.

Summary sentence

Elevated serum BAFF in children with MIS-C supports the state of polyclonal B cell activation and autoimmune phenomena characterizing this disease.

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  1. ScreenIT

    SciScore for 10.1101/2022.05.18.22275245: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Informed consent with participation in this study was signed by the participants’ legal guardians in accordance with the Declaration of Helsinki and the study was approved by the Ethical Committee of the University Hospital in Motol, reference no. EK-1376/21.
    IRB: Informed consent with participation in this study was signed by the participants’ legal guardians in accordance with the Declaration of Helsinki and the study was approved by the Ethical Committee of the University Hospital in Motol, reference no. EK-1376/21.
    Sex as a biological variableIn total, 50 MIS-C patients were recruited during the inclusion period between October 2020 and April 2021, 24 female, age 11 months to 18 years (7.8 ± 4.35 years, mean ± SD).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Flow cytometry measurement was performed on BD FACSLyrics (BD Immunocytometry Systems, San Jose, CA)
    BD Immunocytometry Systems
    suggested: (South Florida University College of Medicine Fred Wright Jr Flow Cytometry Core Facility, RRID:SCR_017901)
    FlowJo software was used for data analysis (TreeStar, Ashland, OR).
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistics: Statistical analysis was performed using using Brown-Forsythe and Welch one-way analysis of variance (ANOVA) and unpaired t-tests with Welch’s correction in GraphPad Prism 8.0 (San Diego, CA, USA).
    GraphPad
    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2022.05.18.22275245v1 on medRxiv