Abnormal antibodies to self-carbohydrates in SARS-CoV-2-infected patients
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Abstract
Our immune system is critical for preventing and treating SARS-CoV-2 infections, but aberrant immune responses can have deleterious effects. While antibodies to glycans could recognize the virus and influence the clinical outcome, little is known about their roles. Using a carbohydrate antigen microarray, we profiled serum antibodies in healthy control subjects and COVID-19 patients from two separate cohorts. COVID-19 patients had numerous autoantibodies to self-glycans, including antiganglioside antibodies that can cause neurological disorders. Additionally, nearly all antiglycan IgM signals were lower in COVID-19 patients, indicating a global dysregulation of this class of antibodies. Autoantibodies to certain N-linked glycans correlated with more severe disease, as did low levels of antibodies to the Forssman antigen and ovalbumin. Collectively, this study indicates that expanded testing for antiglycan antibodies could be beneficial for clinical analysis of COVID-19 patients and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses.
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SciScore for 10.1101/2020.10.15.341479: (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. Table 2: Resources
Antibodies Sentences Resources The bound serum antibodies were detected by incubating with Cy3 anti-Human IgG and DyLight 647 anti-human IgM (Jackson ImmunoResearch) at 3 µg/mL in PBS buffer with 3% BSA and 1% HSA (100 µL/well) under agitation at 37 °C for 2 hours. anti-Human IgGsuggested: Noneanti-human IgMsuggested: NoneEach of the antibody stocks (PGT121, PGT126, PGT128, NIH AIDS Reagent Program) were diluted to 100 µg/mL diluted 5-fold in 1% BSA in PBS buffer. PGT121suggested: (bNAber Cat# bNAberID_24, RRID:AB_2491041)PG…SciScore for 10.1101/2020.10.15.341479: (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. Table 2: Resources
Antibodies Sentences Resources The bound serum antibodies were detected by incubating with Cy3 anti-Human IgG and DyLight 647 anti-human IgM (Jackson ImmunoResearch) at 3 µg/mL in PBS buffer with 3% BSA and 1% HSA (100 µL/well) under agitation at 37 °C for 2 hours. anti-Human IgGsuggested: Noneanti-human IgMsuggested: NoneEach of the antibody stocks (PGT121, PGT126, PGT128, NIH AIDS Reagent Program) were diluted to 100 µg/mL diluted 5-fold in 1% BSA in PBS buffer. PGT121suggested: (bNAber Cat# bNAberID_24, RRID:AB_2491041)PGT126, PGT128suggested: NoneResults 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: We detected the following sentences addressing limitations in the study:Several limitations of this study should be mentioned. First, our glycan microarray only contains a small portion of the glycans found in the human glycome. Thus, there may be other important anti-glycan antibody populations that were not detected. Second, our study included a relatively small cohort of 40 COVID-19 patients and 20 healthy controls. In other work, we have profiled serum anti-glycan antibodies in hundreds of healthy subjects, so our understanding of normal antibody repertoires draws from considerable experience.56, 87 In contrast, these are the first 40 COVID-19 patients we have evaluated, and additional testing will be helpful to more fully investigate the findings in this study. Third, information about patient symptoms and outcome were not available. Consequently, follow up studies will be needed to evaluate potential correlations between symptoms and anti-glycan antibody repertoires. Additional studies to address these limitations are currently underway. Lastly, our study highlights the importance of studying immune responses to carbohydrates. Glycans are one of the major families of antigens found on SARS-CoV-2 and other viruses, but responses to these antigens are often difficult to study. By profiling serum antibodies with a large and diverse carbohydrate antigen microarray, we were able to rapidly identify abnormally high antibodies to a variety of self-glycans. These results provide new insight into the immune response to SARS-CoV-2 and illustrate the ...
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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