Polymorphism in IFNAR contributes to glucocorticoid response and outcome in ARDS and COVID-19
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Abstract
The use of glucocorticoids has given contradictory results for treating acute respiratory distress syndrome (ARDS). Here we report a novel disease association of a SNP rs9984273, which is situated in the interferon alpha/beta receptor (IFNAR2) gene in an area corresponding to a binding motif of the glucocorticoid receptor (GR). The minor allele of SNP rs9984273 associates with higher IFNAR expression, lower IFN-gamma and IL-6 levels and less severe form of coronavirus diseases (COVID-19) according to the COVID-19 Host Genetics Initiative database, and better outcome in interferon (IFN) beta treated patients with ARDS. Thus, the distribution of this SNP within clinical study arms may explain the contradictory results of multiple ARDS studies and outcomes in COVID-19 concerning type I IFN signalling and glucocorticoids.
One-Sentence Summary
Single nucleotide polymorphism in interferon receptor contributes to corticosteroid response and outcome in ARDS and COVID-19
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SciScore for 10.1101/2022.03.10.22272123: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: There were 75 of those patients with an available genetic consent and samples available. Sex as a biological variable not detected. Randomization Shortly, The INTEREST trial was a multi-center, randomized, double-blind, parallel-group trial conducted at 74 intensive care units in 8 European countries (from December 2015 to December 2017) that included 296 adults with moderate to severe ARDS. Blinding The staining intensity of each sample was blindly scored from 1 to 3. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources The first stage antibodies were anti-alpha chain of the IFN alpha/beta receptor (St John’s Laboratory STJ112765) that was used 1:2000 and 1:5000 and … SciScore for 10.1101/2022.03.10.22272123: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: There were 75 of those patients with an available genetic consent and samples available. Sex as a biological variable not detected. Randomization Shortly, The INTEREST trial was a multi-center, randomized, double-blind, parallel-group trial conducted at 74 intensive care units in 8 European countries (from December 2015 to December 2017) that included 296 adults with moderate to severe ARDS. Blinding The staining intensity of each sample was blindly scored from 1 to 3. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources The first stage antibodies were anti-alpha chain of the IFN alpha/beta receptor (St John’s Laboratory STJ112765) that was used 1:2000 and 1:5000 and anti-Stat1 (1:400, 9175S), anti-pStat1(1:100, 9167S) and anti-Stat2 (1:200, 72604S) all from Cell Signalling. anti-Stat1suggested: (Cell Signaling Technology Cat# 9167, RRID:AB_561284)anti-pStat1suggested: (Fluidigm Cat# 3153003A, RRID:AB_2811248)anti-Stat2suggested: (Cell Signaling Technology Cat# 72604, RRID:AB_2799824)Recombinant DNA Sentences Resources All 14 samples were used for staining IFNAR1 and 5 CT and 5 TT samples for Stat1, pStat1 and Stat2 stainings. pStat1suggested: NoneSoftware and Algorithms Sentences Resources Pro-inflammatory cytokine levels were analysed using Bio-Plex Cytokine Assay by Bio-Rad Laboratories (Hercules, USA). Bio-Rad Laboratoriessuggested: (Bio-Rad Laboratories, RRID:SCR_008426)Differences in SNP rs9984273 genotype distribution between deceased and alive ARDS patients were tested using allelic chi-square test using the PLINK software (26). PLINKsuggested: (PLINK, RRID:SCR_001757)The HaploReg tool (28) was used to find matches between the SNP rs9984273 region and the position weight matrices derived from the Encode ChIP-seq data (22). HaploRegsuggested: (HaploReg, RRID:SCR_006796)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: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT00789685 Completed Safety, Tolerability and Preliminary Efficacy of FP-1201 in … NCT02622724 Terminated Efficacy and Safety of FP-1201-lyo (Interferon Beta-1a) in P… 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.
- Thank you for including a protocol registration statement.
Results from scite Reference Check: We found no unreliable references.
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