Proteomic profiling of MIS-C patients indicates heterogeneity relating to interferon gamma dysregulation and vascular endothelial dysfunction
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Abstract
Multi-system Inflammatory Syndrome in Children (MIS-C) is a major complication of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection in pediatric patients. Weeks after an often mild or asymptomatic initial infection with SARS-CoV-2 children may present with a severe shock-like picture and marked inflammation. Children with MIS-C present with varying degrees of cardiovascular and hyperinflammatory symptoms. Here we perform a comprehensive analysis of the plasma proteome of more than 1400 proteins in children with SARS-CoV-2. We hypothesize that the proteome would reflect heterogeneity in hyperinflammation and vascular injury, and further identify pathogenic mediators of disease. We show that protein signatures demonstrate overlap between MIS-C, and the inflammatory syndromes macrophage activation syndrome (MAS) and thrombotic microangiopathy (TMA). We demonstrate that PLA2G2A is an important marker of MIS-C that associates with TMA. We find that IFNγ responses are dysregulated in MIS-C patients, and that IFNγ levels delineate clinical heterogeneity.
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SciScore for 10.1101/2021.04.13.21255439: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study Approvals: This study was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board (IRB) at CHOP.
Consent: Verbal consent for this minimal risk study was obtained from patients or their legally authorized representative.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources All assay validation data are available on the Olink website (www.olink.com). sC5b9 ELISA Assay: sC5b9 levels were determined using enzyme-linked immunosorbent assays (ELISA; Cat. #558315; BD Biosciences, San Jose CA, USA). Cat.suggested:…SciScore for 10.1101/2021.04.13.21255439: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IRB: Study Approvals: This study was conducted in accordance with the Declaration of Helsinki and received approval from the Institutional Review Board (IRB) at CHOP.
Consent: Verbal consent for this minimal risk study was obtained from patients or their legally authorized representative.Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Software and Algorithms Sentences Resources All assay validation data are available on the Olink website (www.olink.com). sC5b9 ELISA Assay: sC5b9 levels were determined using enzyme-linked immunosorbent assays (ELISA; Cat. #558315; BD Biosciences, San Jose CA, USA). Cat.suggested: NoneAll analysis was performed in FlowJo (Treestar, version 10.6.2). FlowJosuggested: (FlowJo, RRID:SCR_008520)General statistical methods: All statistical analyses were performed in R (version 4.0.4) using RStudio (RStudio, PBC, Boston, MA). RStudiosuggested: (RStudio, RRID:SCR_000432)The factoextra package (https://cran.r-project.org/web/packages/factoextra/index.html) was used to extract and visualize PCA elements. https://cran.r-project.org/web/packages/factoextra/index.htmlsuggested: (factoextra, RRID:SCR_016692)We used the KEGG pathway database (https://www.genome.jp/kegg/pathway.html) which includes a manual collection of pathway maps examining a total of 777,729 molecular pathways, with 544 main pathways included. KEGGsuggested: (KEGG, RRID:SCR_012773)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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