Vascular and Non-HLA autoantibody profiles in hospitalized patients with COVID-19

Brian Lichtenstein; Ying Zheng; David Gjertson; Kathie G Ferbas; Anne W Rimoin; Otto O Yang; Grace M Aldrovandi; Joanna M Schaenman; Elaine F Reed; Jennifer A Fulcher

doi:10.3389/fimmu.2023.1197326

Vascular and Non-HLA autoantibody profiles in hospitalized patients with COVID-19

Front Immunol. 2023 Jun 15:14:1197326. doi: 10.3389/fimmu.2023.1197326. eCollection 2023.

Authors

Brian Lichtenstein¹, Ying Zheng², David Gjertson^{2

3}, Kathie G Ferbas⁴, Anne W Rimoin⁵, Otto O Yang⁶, Grace M Aldrovandi⁴, Joanna M Schaenman⁶, Elaine F Reed², Jennifer A Fulcher^{6

7}

Affiliations

¹ Division of Hospital Medicine, Department of Internal Medicine, Sharp Rees-Stealy Medical Group, Sharp Healthcare, San Diego, CA, United States.
² Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
³ Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, United States.
⁴ Division of Infectious Diseases, Department of Pediatrics, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
⁵ Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, United States.
⁶ Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States.
⁷ Infectious Diseases Section, Veterans Affairs (VA) Greater Los Angeles Healthcare System, Los Angeles, CA, United States.

Abstract

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.

Keywords: Anti-endothelial antibodies; COVID-19; Non-HLA antigens; angiotensin II receptor type 1 (AT1R); autoantibody.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autoantibodies*
Autoimmunity
COVID-19*
Endothelial Cells
Humans
Risk Factors

Substances

Autoantibodies

Grants and funding

This work was supported by the UCLA David Geffen School of Medicine – Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award to JF and Sharp HealthCare Foundation to BL. JF is also supported in part by the Doris Duke Foundation award #2019086.