Favourable antibody responses to human coronaviruses in children and adolescents with autoimmune rheumatic diseases
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Abstract
Differences in humoral immunity to coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), between children and adults remain unexplained and the impact of underlying immune dysfunction or suppression unknown. Here, we examined the antibody immune competence of children and adolescents with prevalent inflammatory rheumatic diseases, juvenile idiopathic arthritis (JIA), juvenile dermatomyositis (JDM) and juvenile systemic lupus erythematosus (JSLE), against the seasonal human coronavirus (HCoV)-OC43 that frequently infects this age group. Despite immune dysfunction and immunosuppressive treatment, JIA, JDM and JSLE patients mounted comparable or stronger responses than healthier peers, dominated by IgG antibodies to HCoV-OC43 spike, and harboured IgG antibodies that cross-reacted with SARS-CoV-2 spike. In contrast, responses to HCoV-OC43 and SARS-CoV-2 nucleoproteins exhibited delayed age-dependent class-switching and were not elevated in JIA, JDM and JSLE patients, arguing against increased exposure. Consequently, autoimmune rheumatic diseases and their treatment were associated with a favourable ratio of spike to nucleoprotein antibodies.
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SciScore for 10.1101/2021.02.15.431291: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication Contamination: Cell lines and plasmids: HEK293T cells and Vero E6 were obtained from the Cell Services facility at The Francis Crick Institute and verified as mycoplasma-free. Table 2: Resources
Antibodies Sentences Resources Patients were treated as being ‘autoantibody positive’ if any of rheumatoid factor (RF), anti-nuclear antibodies (ANA) or myositis-specific/myositis-associated autoantibodies were recorded as positive. anti-nuclearsuggested: NoneFlow cytometric detection of antibodies to spike and envelope … SciScore for 10.1101/2021.02.15.431291: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable not detected. Cell Line Authentication Contamination: Cell lines and plasmids: HEK293T cells and Vero E6 were obtained from the Cell Services facility at The Francis Crick Institute and verified as mycoplasma-free. Table 2: Resources
Antibodies Sentences Resources Patients were treated as being ‘autoantibody positive’ if any of rheumatoid factor (RF), anti-nuclear antibodies (ANA) or myositis-specific/myositis-associated autoantibodies were recorded as positive. anti-nuclearsuggested: NoneFlow cytometric detection of antibodies to spike and envelope glycoproteins: HEK293T cells expressing HCoV-OC43 spike were mixed with cells expressing ERV3-1 envelope glycoprotein and GFP and HEK293T cells expressing SARS-CoV-2 spike were mixed with cells expressing HERV-K113 envelope glycoprotein and GFP at equal rations. ERV3-1 envelope glycoproteinsuggested: NoneGFPsuggested: NoneHERV-K113 envelope glycoproteinsuggested: None, APC anti-IgM (clone MHM-88, Biolegend) and PE anti-IgA (clone IS11-8E10, Miltenyi Biotech) for 30 min (all antibodies diluted 1:200 in FACS buffer). anti-IgMsuggested: Noneanti-IgAsuggested: NoneFlow cytometric detection of antibodies to nucleoproteins: Aliquots of recombinant HCoV-OC43 and SARS-CoV-2 nucleoproteins were conjugated with aldehyde functionalized polymethylmethacrylate-based microspheres (PolyAn GmbH, Berlin, Germany), according to manufacturer’s instructions, and kept at 4°C until use. PolyAn GmbH , Berlin , Germanysuggested: NoneOutcome variables modelled were the total, IgG and IgA antibody levels for SARS-CoV-2 and OC43 spike proteins and nucleoproteins. total, IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources Cell lines and plasmids: HEK293T cells and Vero E6 were obtained from the Cell Services facility at The Francis Crick Institute and verified as mycoplasma-free. Vero E6suggested: RRID:CVCL_XD71)Beads were then stained with serum and plasma samples, as described above for HEK293T cells used in flow cytometric detection of antibodies to spike and envelope glycoproteins. HEK293Tsuggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)Software and Algorithms Sentences Resources Samples were run on a Ze5 analyzer (Bio-Rad) running Bio-Rad Everest software v2.4 or an LSR Fortessa with a high-throughput sampler (BD Biosciences) running BD FACSDiva software v8.0, and analyzed using FlowJo v10 Bio-Rad Everestsuggested: NoneBD FACSDivasuggested: (BD FACSDiva Software, RRID:SCR_001456)FlowJosuggested: (FlowJo, RRID:SCR_008520)Virus plaques were quantified and IC50 values were calculated using LabView software as described previously (35) or SigmaPlot v14.0 (Systat Software). LabViewsuggested: (LabView , RRID:SCR_014325)Statistical analyses: Data were analysed and plotted in GraphPad Prism v8 (GraphPad Software) or SigmaPlot v14.0 (Systat Software). GraphPad Prismsuggested: (GraphPad Prism, RRID:SCR_002798)GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)SigmaPlotsuggested: (SigmaPlot, RRID:SCR_003210)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.
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