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Single-cell Analysis of Immunophenotype and Cytokine Production in Peripheral Whole Blood via Mass Cytometry
Published on: June 26, 2018
Immune complexome analysis reveals an autoimmune signature predictive of COVID-19 severity
Marino Moriishi1, Takahiro Takazono2, Junya Hashizume3
1Department of Pharmacy Practice, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Insights
Severe COVID-19 is not linked to immune complex levels, but specific human protein antigens within them can predict disease severity. This discovery may aid in diagnosing and treating severe cases.
Area of Science:
- Immunology
- Infectious Diseases
- Biochemistry
Background:
- Factors influencing severe COVID-19 (coronavirus disease 2019) remain unclear.
- Immune complexes (ICs) are implicated in COVID-19 severity, but their antigens are uncharacterized.
Purpose of the Study:
- To investigate the role of ICs and their antigens in COVID-19 severity.
- To characterize antigens within ICs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients.
Main Methods:
- Used C1q ELISA and immune complexome analysis on sera from 64 unvaccinated COVID-19 patients.
- Categorized patients into severe (n=35) and non-severe (n=28) groups based on symptoms.
Main Results:
- Neither serum IC concentration nor the number of IC antigens correlated with COVID-19 severity.
- Identified six specific human protein antigens (haptoglobin, serum amyloid A-1/A-2, clusterin, lipopolysaccharide-binding protein, complement factor H-related protein 3) enriched in severe cases.
- These six antigens accurately predicted COVID-19 severity (AUC=0.90, sensitivity=94%, specificity=79%).
- No association found between COVID-19 severity and SARS-CoV-2 derived IC antigens.
Conclusions:
- An identified signature of six IC antigens may aid in diagnosing and treating severe COVID-19.
- This finding highlights specific human protein ICs as potential biomarkers for severe disease.
Background:
The factors contributing to the development of severe coronavirus disease 2019 (COVID-19) following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain unclear. Although the presence of immune complexes (ICs), formed between antibodies and their antigens, has been linked to COVID-19 severity, their role requires further investigation, and the antigens within these ICs are yet to be characterized.
Method:
Here, a C1q enzyme-liked immunosorbent assay and immune complexome analysis were used to determine IC concentrations and characterize IC antigens, respectively, in the sera of 64 unvaccinated COVID-19 patients with PCR-confirmed SARS-CoV-2 infection, enrolled at seven participating centers in 2020. For the analysis, the patients were split into the severe (n = 35) and non-severe (n = 28) groups on the basis of their COVID-19 symptoms.
Results:
We found that neither serum IC concentration nor IC antigen number was associated with COVID-19 severity. However, we identified six IC antigens, which were significantly enriched in the severe versus non-severe group. These IC antigens were all derived from human proteins, namely haptoglobin, the serum amyloid A-2 protein, the serum amyloid A-1 protein, clusterin, and lipopolysaccharide-binding protein, and complement-factor-H-related protein 3. Meanwhile, we found no association between COVID-19 severity and IC antigens derived from SARS-CoV-2 proteins. Collectively, the six IC antigens predicted COVID-19 severity with a moderate degree of accuracy (area under the receiver operating characteristic curve = 0.90, sensitivity = 94 %, specificity = 79 %).
Conclusions:
The IC antigen signature identified in this study may have important implications for the diagnosis and treatment of severe COVID-19.
