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Broad auto-reactive IgM responses are common in critically ill patients, including those with COVID-19.
Wong, Andrew Kam Ho; Woodhouse, Isaac; Schneider, Frank; Kulpa, Deanna A; Silvestri, Guido; Maier, Cheryl L.
  • Wong AKH; Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Woodhouse I; Centre for Cellular and Molecular Physiology, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Schneider F; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
  • Kulpa DA; Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Silvestri G; Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
  • Maier CL; Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.
Cell Rep Med ; 2(6): 100321, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1253745
Semantic information from SemMedBD (by NLM)
1. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
2. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
3. Immunoglobulin M NEG_PART_OF Patients
Subject
Immunoglobulin M
Predicate
NEG_PART_OF
Object
Patients
4. Endothelium PART_OF Lung
Subject
Endothelium
Predicate
PART_OF
Object
Lung
5. Microarray Analysis USES Proteome
Subject
Microarray Analysis
Predicate
USES
Object
Proteome
6. Plasma membrane LOCATION_OF Immunoglobulin M
Subject
Plasma membrane
Predicate
LOCATION_OF
Object
Immunoglobulin M
7. Critical Illness PROCESS_OF Patients
Subject
Critical Illness
Predicate
PROCESS_OF
Object
Patients
8. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
9. Immunoglobulin M NEG_PART_OF Patients
Subject
Immunoglobulin M
Predicate
NEG_PART_OF
Object
Patients
10. Endothelium PART_OF Lung
Subject
Endothelium
Predicate
PART_OF
Object
Lung
11. Microarray Analysis USES Proteome
Subject
Microarray Analysis
Predicate
USES
Object
Proteome
12. Plasma membrane LOCATION_OF Immunoglobulin M
Subject
Plasma membrane
Predicate
LOCATION_OF
Object
Immunoglobulin M
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.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Autoantibodies / Immunoglobulin M / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Rep Med Year: 2021 Document Type: Article Affiliation country: J.xcrm.2021.100321

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Autoantibodies / Immunoglobulin M / COVID-19 Type of study: Prognostic study Limits: Humans Language: English Journal: Cell Rep Med Year: 2021 Document Type: Article Affiliation country: J.xcrm.2021.100321