Pulmonary Surfactant Proteins Are Inhibited by Immunoglobulin A Autoantibodies in Severe COVID-19

  1. Tobias Sinnberg
  2. Christa Lichtensteiger
  3. Omar Hasan Ali
  4. Oltin T. Pop
  5. Ann-Kristin Jochum
  6. Lorenz Risch
  7. Silvio D. Brugger
  8. Ana Velic
  9. David Bomze
  10. Philipp Kohler
  11. Pietro Vernazza
  12. Werner C. Albrich
  13. Christian R. Kahlert
  14. Marie-Therese Abdou
  15. Nina Wyss
  16. Kathrin Hofmeister
  17. Heike Niessner
  18. Carl Zinner
  19. Mara Gilardi
  20. Alexandar Tzankov
  21. Martin Röcken
  22. Alex Dulovic
  23. Srikanth Mairpady Shambat
  24. Natalia Ruetalo
  25. Philipp K. Buehler
  26. Thomas C. Scheier
  27. Wolfram Jochum
  28. Lukas Kern
  29. Samuel Henz
  30. Tino Schneider
  31. Gabriela M. Kuster
  32. Maurin Lampart
  33. Martin Siegemund
  34. Roland Bingisser
  35. Michael Schindler
  36. Nicole Schneiderhan-Marra
  37. Hubert Kalbacher
  38. Kathy D. McCoy
  39. Werner Spengler
  40. Martin H. Brutsche
  41. Boris Maček
  42. Raphael Twerenbold
  43. Josef M. Penninger
  44. Matthias S. Matter
  45. Lukas Flatz

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Abstract

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  1. Version published to 10.1164/rccm.202201-0011oc
  2. ScreenIT

    SciScore for 10.1101/2021.02.02.21250940: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Clinical study: patient recruitment, data and blood sample collection: Patient data and blood collection was approved by the Ethics committee of Eastern Switzerland (study ID 2020-01006), and tissue collection by Ethics committee of Northern and Central Switzerland (study ID 2020-00969).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Infection of asymptomatic COVID-19 was confirmed with serology of SARS-CoV-2 antibodies, using two independent antibody tests: SGIT flex Covid 19, a lateral flow immunochromatographic assay (LFIA) (Sugentech, Daejeon, South Korea), and Elecsys Anti-SARS-CoV-2, an electro-chemiluminescence immunoassay (ECLIA) (Roche International Diagnostics AG, Rotkreuz, Switzerland).
    Anti-SARS-CoV-2
    suggested: None
    Antibody analysis: Myositis and systemic sclerosis antibodies (i.e. Mi-2a, Mi-2b, TIF1g, MDA5, NXP2, SAE1, Ku, PM- SCL100, PM-SCL75, Jo-1, SRP, PL-7, PL-12, EJ, OJ, Ro5 for myositis; Scl-70, CENPA, CENPB, RP11 (RNAP-III), RP155 (RNAP-III)
    MDA5
    suggested: None
    NXP2
    suggested: None
    SAE1
    suggested: None
    Jo-1
    suggested: (GenWay Biotech Inc. Cat# GWB-T00081, RRID:AB_11161521)
    CENPB
    suggested: None
    RP11
    suggested: None
    Autoantibodies against Cardiolipin, β-2-glycoprotein 1, double stranded DNA (dsDNA), cyclic citrullinated peptide (CCP), SSA1, SSA2, SSB, Sm, PR3, and MPO were determined by fluorescence enzyme immunoassay on a Unicap 250 analyzer (Thermo Fisher Scientific, Waltham, U.S.A.)
    double stranded DNA ( dsDNA)
    suggested: (DSHB Cat# autoanti-dsDNA, RRID:AB_10805293)
    dsDNA
    suggested: None
    cyclic citrullinated peptide ( CCP)
    suggested: None
    CCP
    suggested: None
    SSA1
    suggested: None
    SSB
    suggested: None
    PR3
    suggested: None
    MPO
    suggested: None
    37-39 Briefly, anti-surfactant (diluted 1:100 ab51891, Abcam), anti-IgA FITC and anti-IgG FITC primary antibodies (diluted 1:50, respectively F0316-F0202 Dako) were used.
    anti-surfactant
    suggested: (Abcam Cat# ab51891, RRID:AB_882674)
    anti-IgA FITC
    suggested: None
    anti-IgG FITC
    suggested: None
    Staining using anti-SFTPB antibodies diluted 1:100 (NCL-SPPB) was done in blocking buffer for 1h at RT.
    anti-SFTPB
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Antibody analysis: Myositis and systemic sclerosis antibodies (i.e. Mi-2a, Mi-2b, TIF1g, MDA5, NXP2, SAE1, Ku, PM- SCL100, PM-SCL75, Jo-1, SRP, PL-7, PL-12, EJ, OJ, Ro5 for myositis; Scl-70, CENPA, CENPB, RP11 (RNAP-III), RP155 (RNAP-III)
    MDA5
    suggested: None
    Software and Algorithms
    SentencesResources
    Differential expression analysis was conducted in R version 4.0.3 (R Project for Statistical Computing, Vienna, Austria) with the DESeq2 package using default settings.
    R Project for Statistical
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)
    DESeq2
    suggested: (DESeq, RRID:SCR_000154)
    The heatmap of genes with a | log fold change | > 1 was produced with the complexHeatmap package.
    complexHeatmap
    suggested: (ComplexHeatmap, RRID:SCR_017270)
    All genes in the autoimmune panel were pre-ranked using the Wald test statistic and submitted to the entire KEGG database of human pathways using the clusterProfiler package.
    KEGG
    suggested: (KEGG, RRID:SCR_012773)
    clusterProfiler
    suggested: (clusterProfiler, RRID:SCR_016884)
    Images were analyzed using QuPath software40 as previously reported.
    QuPath
    suggested: (QuPath, RRID:SCR_018257)
    Single cell RNA data analysis: Single-cell RNA sequencing data of healthy lungs were obtained from the LungMap project31 via the ToppCell portal (https://toppcell.cchmc.org/).
    LungMap
    suggested: (LungMap, RRID:SCR_016347)
    The MS data was processed with MaxQuant software suite v.1.6.7.045 to measure the iBAQ which was used to calculate the relative protein level (riBAQ=iBAQ/(ΣiBAQ)).
    MaxQuant
    suggested: (MaxQuant, RRID:SCR_014485)

    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.

  3. Version published to 10.1101/2021.02.02.21250940v2 on medRxiv
  4. Version published to 10.1101/2021.02.02.21250940v1 on medRxiv