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Endothelial Cell–Activating Antibodies in COVID‐19
Author(s) -
Shi Hui,
Zuo Yu,
Navaz Sherwin,
Harbaugh Alyssa,
Hoy Claire K.,
Gandhi Alex A.,
Sule Gautam,
Yalavarthi Srilakshmi,
Gockman Kelsey,
Madison Jacqueline A.,
Wang Jintao,
Zuo Melanie,
Shi Yue,
Maile Michael D.,
Knight Jason S.,
Kanthi Yogendra
Publication year - 2022
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.42094
Subject(s) - endothelial activation , cell adhesion molecule , immunology , endothelial stem cell , antibody , soluble cell adhesion molecules , endothelial dysfunction , intercellular adhesion molecule 1 , cell adhesion , endothelium , context (archaeology) , medicine , autoantibody , intercellular adhesion molecule , cell , chemistry , biology , inflammation , biochemistry , in vitro , paleontology
Objective While endothelial dysfunction has been implicated in the widespread thromboinflammatory complications of COVID‐19, the upstream mediators of endotheliopathy remain, for the most part, unknown. This study was undertaken to identify circulating factors contributing to endothelial cell activation and dysfunction in COVID‐19. Methods Human endothelial cells were cultured in the presence of serum or plasma from 244 patients hospitalized with COVID‐19 and plasma from 100 patients with non–COVID‐19–related sepsis. Cell adhesion molecules (E‐selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1 [ICAM‐1]) were quantified using in‐cell enzyme‐linked immunosorbent assay. Results Serum and plasma from COVID‐19 patients increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM‐1 and E‐selectin were elevated in patient serum and correlated with disease severity. The presence of circulating antiphospholipid antibodies was a strong marker of the ability of COVID‐19 serum to activate endothelium. Depletion of total IgG from antiphospholipid antibody–positive serum markedly reduced the up‐regulation of cell adhesion molecules. Conversely, supplementation of control serum with patient IgG was sufficient to trigger endothelial activation. Conclusion These data are the first to indicate that some COVID‐19 patients have potentially diverse antibodies that drive endotheliopathy, providing important context regarding thromboinflammatory effects of autoantibodies in severe COVID‐19.