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Vascular and Non-HLA autoantibody profiles in hospitalized patients with COVID-19
Brian Lichtenstein1, Ying Zheng2, David Gjertson2,3
1Division of Hospital Medicine, Department of Internal Medicine, Sharp Rees-Stealy Medical Group, Sharp Healthcare, San Diego, CA, United States.
Insights
Autoantibodies against various proteins were found in hospitalized COVID-19 patients. However, these autoantibodies did not directly correlate with COVID-19 severity, suggesting a complex role in the disease.
Area of Science:
- Immunology
- Infectious Diseases
- Autoimmunity
Background:
- Severe COVID-19 is linked to immune hyperactivation.
- Autoantibodies against vascular, tissue, and cytokine targets are present in COVID-19 patients.
- The correlation between autoantibodies and COVID-19 severity requires further investigation.
Purpose of the Study:
- To investigate the expression of vascular and non-HLA autoantibodies in hospitalized COVID-19 patients.
- To examine the relationship between autoantibodies and COVID-19 severity and clinical risk factors.
Main Methods:
- Exploratory study of 110 hospitalized COVID-19 patients (moderate to critical illness).
- Analysis of autoantibodies against vascular and non-HLA autoantigens.
- Logistic regression used to assess relationships with severity and risk factors.
Main Results:
- No significant differences in autoantibodies against angiotensin II receptor type 1 (AT1R) or endothelial cells based on COVID-19 severity.
- Seven autoantibodies (myosin, shc3, perc, gdnf, eno1, lphn1, coll6) showed differences in expression related to severity.
- Greater breadth and higher expression of these seven autoantibodies were observed in less severe COVID-19 cases.
Conclusions:
- Hospitalized COVID-19 patients exhibit auto-reactive antibodies targeting endothelial cells, angiotensin II receptors, and structural proteins.
- Phenotypic severity of COVID-19 did not directly correlate with specific autoantibodies.
- Further research is crucial to understand the role of autoimmunity in COVID-19 pathogenesis and long-term effects.
Introduction:
Severe COVID-19 illness is characterized by an overwhelming immune hyperactivation. Autoantibodies against vascular, tissue, and cytokine antigens have been detected across the spectrum of COVID-19. How these autoantibodies correlate with COVID-19 severity is not fully defined.
Methods:
We performed an exploratory study to investigate the expression of vascular and non-HLA autoantibodies in 110 hospitalized patients with COVID-19 ranging from moderate to critically ill. Relationships between autoantibodies and COVID- 19 severity and clinical risk factors were examined using logistic regression analysis.
Results:
There were no absolute differences in levels of expression of autoantibodies against angiotensin II receptor type 1 (AT1R) or endothelial cell proteins between COVID-19 severity groups. AT1R autoantibody expression also did not differ by age, sex, or diabetes status. Using a multiplex panel of 60 non- HLA autoantigens we did identify seven autoantibodies that differed by COVID-19 severity including myosin (myosin; p=0.02), SHC-transforming protein 3 (shc3; p=0.07), peroxisome proliferator-activated receptor gamma coactivator 1-beta (perc; p=0.05), glial-cell derived neurotrophic factor (gdnf; p=0.07), enolase 1 (eno1; p=0.08), latrophilin-1 (lphn1; p=0.08), and collagen VI (coll6; p=0.05) with greater breadth and higher expression levels seen in less severe COVID-19.
Discussion:
Overall, we found that patients hospitalized with COVID-19 demonstrate evidence of auto-reactive antibodies targeting endothelial cells, angiotensin II receptors, and numerous structural proteins including collagens. Phenotypic severity did not correlate with specific autoantibodies. This exploratory study underscores the importance of better understanding of the role of autoimmunity in COVID-19 disease and sequelae.
