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Broad Auto-Reactive IgM Responses Are Common In Critically Ill COVID-19 Patients.

ABSTRACT: The pathogenesis of severe COVID-19 remains poorly understood. While several studies suggest that immune dysregulation plays a central role, the key mediators of this process are yet to be defined. Here, we demonstrate that plasma from a high proportion (77%) of critically ill COVID-19 patients, but not healthy controls, contains broadly auto-reactive immunoglobulin M (IgM), and only infrequently auto-reactive IgG or IgA. Importantly, these auto-IgM preferentially recognize primary human lung cells in vitro, including pulmonary endothelial and epithelial cells. By using a combination of flow cytometry, LDH-release assays, and analytical proteome microarray technology, we identified high-affinity, complement-fixing, auto-reactive IgM directed against 263 candidate auto-antigens, including numerous molecules preferentially expressed on cellular membranes in pulmonary, vascular, gastrointestinal, and renal tissues. These findings suggest that broad IgM-mediated autoimmune reactivity may be involved in the pathogenesis of severe COVID-19, thereby identifying a potential target for novel therapeutic interventions.

SUBMITTER: Maier C

PROVIDER: S-EPMC7781325 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Broad auto-reactive IgM responses are common in critically ill patients, including those with COVID-19.

Project description:The pathogenesis of severe coronavirus disease 2019 (COVID-19) remains poorly understood. While several studies suggest that immune dysregulation plays a central role, the key mediators of this process are yet to be defined. Here, we demonstrate that plasma from a high proportion (93%) of critically ill COVID-19 patients, but not healthy controls, contains broadly auto-reactive immunoglobulin M (IgM) and less frequently auto-reactive IgG or IgA. Importantly, these auto-IgMs preferentially recognize primary human lung cells in vitro, including pulmonary endothelial and epithelial cells. By using a combination of flow cytometry, analytical proteome microarray technology, and lactose dehydrogenase (LDH)-release cytotoxicity assays, we identify high-affinity, complement-fixing, auto-reactive IgM directed against 260 candidate autoantigens, including numerous molecules preferentially expressed on the cellular membranes of pulmonary, vascular, gastrointestinal, and renal tissues. These findings suggest that broad IgM-mediated autoimmune reactivity may be involved in the pathogenesis of severe COVID-19, thereby identifying a potential target for therapeutic interventions.

| S-EPMC8160082 | biostudies-literature

Transcriptomic clustering of critically-ill COVID-19 patients

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-02-28 | GSE197259 | GEO

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Transcriptomic clustering of critically-ill COVID-19 patients [Day 1-RNA-Seq]

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Pulmonary Procoagulant and Innate Immune Responses in Critically Ill COVID-19 Patients.

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2021-07-03 | GSE168400 | GEO

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2021-12-10 | PXD029547 | Pride

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| S-EPMC8286043 | biostudies-literature

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