Autoantibodies against interleukin-1 receptor antagonist in multisystem inflammatory syndrome in children: a multicentre, retrospective, cohort study

  1. Jochen Pfeifer
  2. Bernhard Thurner
  3. Christoph Kessel
  4. Natalie Fadle
  5. Parastoo Kheiroddin
  6. Evi Regitz
  7. Marie-Christin Hoffmann
  8. Igor Age Kos
  9. Klaus-Dieter Preuss
  10. Yvan Fischer
  11. Klaus Roemer
  12. Stefan Lohse
  13. Kristina Heyne
  14. Marie-Claire Detemple
  15. Michael Fedlmeier
  16. Hendrik Juenger
  17. Harald Sauer
  18. Sascha Meyer
  19. Tilman Rohrer
  20. Helmut Wittkowski
  21. Sören L Becker
  22. Katja Masjosthusmann
  23. Robert Bals
  24. Stephan Gerling
  25. Sigrun Smola
  26. Moritz Bewarder
  27. Einat Birk
  28. Andre Keren
  29. Michael Böhm
  30. André Jakob
  31. Hashim Abdul-Khaliq
  32. Jordi Anton
  33. Michael Kabesch
  34. Rosa Maria Pino-Ramirez
  35. Dirk Foell
  36. Lorenz Thurner

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Abstract

No abstract available

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  1. Version published to 10.1016/s2665-9913(22)00064-9
  2. ScreenIT

    SciScore for 10.1101/2021.09.08.21263027: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the local Ethical Review Board (41/21) and conducted according to the Declaration of Helsinki.
    Consent: Blood Plasma samples of patients with PIMS/MIS-C according were taken after written informed consent in the department of Pediatric Cardiology of the Saarland University Hospital (Homburg/Saar, Germany), the Department of Pediatrics, Klinikum Saarbrücken (Germany), the Department of Pediatric Rheumatology and Immunology of the University Children’s Hospital Muenster (Germany), the Department of Pediatrics, Hospital Sant Joan de
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    All patients with PIMS/MIS-C fulfilled the WHO criteria, in addition all patients were seropositive for antibodies against SARS-CoV-2 or had positive PCR, with the exception of one patient who had only reported contact to SARS-CoV2.
    SARS-CoV-2
    suggested: None
    SARS-CoV2
    suggested: None
    ELISA for autoantibodies against PGRN, IL-1-Ra: The ELISA for autoantibodies was performed as previously described (19).
    PGRN
    suggested: None
    Recombinant IL-1-Ra at 40ng/mL (Biozol, #PPT-AF-2000-01RA) alone or with either anti-IL-1-Ra antibody at 5 µg/mL (antibodies-online#ABIN2856394), recombinant SLP-antibody at 5µg/mL (abcam, #ab191883), plasma diluted 1:20 of a patient with acute PIMS/MIS-C and high-titered IL-1-Ra-antibodies (PIMS-I), or plasma diluted 1:20 of the same patient 7 months after PIMS/MIS-C without anymore detectable IL-1-Ra-Abs were preincubated for 2h at room temperature.
    #PPT-AF-2000-01RA
    suggested: None
    anti-IL-1-Ra
    suggested: None
    antibodies-online#ABIN2856394
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    In short, the antigens were obtained using the coding sequences of the GRN gene encoding PGRN, isoform 1 precursor of IL1RN were recombinantly expressed with a C-terminal FLAG-tag in HEK293 cells under the control of a cytomegalovirus promoter (pSFI).
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)

    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: We detected the following sentences addressing limitations in the study:
    The relatively small number of cases included in the present study, due to the rarity of the disease, is a limitation. Nonetheless, these antibodies suggest to be pathogenetically relevant and should be further investigated in PIMS/MIS-C and other hyperinflammatory diseases.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

  3. Version published to 10.1101/2021.09.08.21263027v1 on medRxiv