Broad auto-reactive IgM responses are common in critically ill patients, including those with COVID-19.
Cell Rep Med
; 2(6): 100321, 2021 06 15.
Article
in English
| MEDLINE | ID: covidwho-1253745
ABSTRACT
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Autoantibodies
/
Immunoglobulin M
/
COVID-19
Limits:
Humans
Language:
English
Journal:
Cell Rep Med
Year:
2021
Document Type:
Article
Affiliation country:
J.xcrm.2021.100321
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