ABO blood group is involved in the quality of the specific immune response

  1. Sergio Gil-Manso
  2. Iria Miguens Blanco
  3. Bruce Motyka
  4. Anne Halpin
  5. Rocio Lopez-Esteban
  6. Veronica A. Perez-Fernandez
  7. Diego Carbonell
  8. Luis Andrés López-Fernández
  9. Lori West
  10. Rafael Correa-Rocha
  11. Marjorie Pion

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Abstract

Since December 2019, the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. To eradicate it, it is crucial to acquire a strong and long-lasting anti-SARS-CoV-2 immunity, by either natural infection or vaccination. We collected blood samples 12–305 days after positive polymerase chain reactions (PCRs) from 35 recovered individuals infected by SARS-CoV-2. Peripheral blood mononuclear cells were stimulated with SARS-CoV-2-derived peptide pools, such as the Spike (S), Nucleocapsid (N), and Membrane (M) proteins, and we quantified anti-S immunoglobulins in plasma. After 10 months post-infection, we observed a sustained SARS-CoV-2-specific CD4+ T-cell response directed against M-protein, but responses against S- or N-proteins were lost over time. Besides, we demonstrated that A-group individuals presented significantly higher frequencies of specific CD4+ T-cell responses against Pep-M than O-group individuals. The A-group subjects also needed longer to clear the virus and they lost cellular immune responses over time, compared to the O-group individuals, who showed a persistent specific immune response against SARS-CoV-2. Therefore, the S-specific immune response was lost over time, and individual factors determine the sustainability of the body’s defences, which must be considered in the future design of vaccines to achieve continuous anti-SARS-CoV-2 immunity.

Summary

This work describes that cellular responses against SARS-CoV-2 M-protein can be detected after 10 months but were lost against S- and N-proteins. Moreover, the individual factors; ABO-group and age influence the sustainability of the specific humoral and cellular immunity against SARS-CoV-2.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.23.445114: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Informed consent was obtained under the Declaration of Helsinki protocol.
    IACUC: The study was approved by the local ethics committee and performed according to their guidelines (COV1-20-007).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Two positive controls for activation were used: PepTivator against cytomegalovirus (Pep-CMV, Miltenyi Biotec), which consisted of 15-mer peptides with 11 amino acids, covering the complete sequence of the pp65 protein of human cytomegalovirus, and CytoStim (Miltenyi Biotec), an antibody-based component that acts similarly to a superantigen of the T-cell receptor.
    PepTivator against cytomegalovirus (Pep-CMV, Miltenyi Biotec)
    suggested: None
    Testing for ABO and SARS-CoV-2 antibodies using Luminex single-antigen beads: ABO-A and ABO-B subtype glycans I–VI were conjugated to bovine serum albumin (BSA), as previously described (Jeyakanthan et al., 2016), and an optimized protein-coupling procedure was used to link each subtype antigen to individual Luminex beads (Angeloni et al., 2018).
    SARS-CoV-2
    suggested: None
    ABO-B subtype glycans I–VI
    suggested: None
    Bound IgM monoclonal antibody was detected with PE-labelled goat anti-mouse IgM secondary antibody (Southern Biotech, Birmingham, AL, US) (Halpin et al., 2018).
    anti-mouse IgM
    suggested: None
    Coupling was confirmed using a rabbit IgG anti-SARS-CoV-2 Spike monoclonal antibody (Sino Biological) and PE-conjugated goat anti-rabbit IgG secondary antibody (Southern Biotech).
    rabbit IgG
    suggested: None
    To detect serum ABO and SARS-CoV-2 antibodies, sera (25-fold dilution) were incubated with Luminex beads for 30 minutes at room temperature, washed, and then incubated with a 50-fold dilution of PE-conjugated goat anti-human IgM or IgG (both from Thermo Fisher, Waltham, MA, US) for 30 minutes at room temperature.
    PE-conjugated goat anti-human IgM
    suggested: None
    IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    All the cytometry data were analysed using the Kaluza software (Beckman Coulter).
    Kaluza
    suggested: (Kaluza, RRID:SCR_016182)
    Graphs were plotted using the GraphPad Prism 7.00 software.
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Statistical analyses were conducted using GraphPad Prism 7.00 and the SPSS (IBM, version 25, Armonk, NY, US) software.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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: Please consider improving the rainbow (“jet”) colormap(s) used on pages 28 and 29. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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

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  2. Version published to 10.1101/2021.05.23.445114v1 on bioRxiv