tetano
Editor, Senior Moderator
Arthritis Rheumatol
. 2022 Feb 17.
doi: 10.1002/art.42094. Online ahead of print.
Endothelial cell-activating antibodies in COVID-19
Hui Shi[SUP] 1 2 [/SUP], Yu Zuo[SUP] 1 [/SUP], Sherwin Navaz[SUP] 1 [/SUP], Alyssa Harbaugh[SUP] 1 [/SUP], Claire K Hoy[SUP] 1 [/SUP], Alex A Gandhi[SUP] 1 [/SUP], Gautam Sule[SUP] 1 [/SUP], Srilakshmi Yalavarthi[SUP] 1 [/SUP], Kelsey Gockman[SUP] 1 [/SUP], Jacqueline A Madison[SUP] 1 [/SUP], Jintao Wang[SUP] 3 [/SUP], Melanie Zuo[SUP] 4 [/SUP], Yue Shi[SUP] 5 [/SUP], Michael D Maile[SUP] 6 7 [/SUP], Jason S Knight[SUP] 1 [/SUP], Yogendra Kanthi[SUP] 3 8 [/SUP]
Affiliations
Abstract
Objective: While endothelial dysfunction has been implicated in the widespread thrombo-inflammatory complications of coronavirus disease-19 (COVID-19), the upstream mediators of endotheliopathy remain for the most part cryptic. Our aim was 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 sepsis. Cell adhesion molecules (E-selectin, VCAM-1, and ICAM-1) were quantified by in-cell ELISA.
Results: Serum and plasma from patients with COVID-19 increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and tracked 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 restrained upregulation 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 suggest that some patients with COVID-19 have potentially diverse antibodies that drive endotheliopathy, adding important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19.
. 2022 Feb 17.
doi: 10.1002/art.42094. Online ahead of print.
Endothelial cell-activating antibodies in COVID-19
Hui Shi[SUP] 1 2 [/SUP], Yu Zuo[SUP] 1 [/SUP], Sherwin Navaz[SUP] 1 [/SUP], Alyssa Harbaugh[SUP] 1 [/SUP], Claire K Hoy[SUP] 1 [/SUP], Alex A Gandhi[SUP] 1 [/SUP], Gautam Sule[SUP] 1 [/SUP], Srilakshmi Yalavarthi[SUP] 1 [/SUP], Kelsey Gockman[SUP] 1 [/SUP], Jacqueline A Madison[SUP] 1 [/SUP], Jintao Wang[SUP] 3 [/SUP], Melanie Zuo[SUP] 4 [/SUP], Yue Shi[SUP] 5 [/SUP], Michael D Maile[SUP] 6 7 [/SUP], Jason S Knight[SUP] 1 [/SUP], Yogendra Kanthi[SUP] 3 8 [/SUP]
Affiliations
- PMID: 35174669
- DOI: 10.1002/art.42094
Abstract
Objective: While endothelial dysfunction has been implicated in the widespread thrombo-inflammatory complications of coronavirus disease-19 (COVID-19), the upstream mediators of endotheliopathy remain for the most part cryptic. Our aim was 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 sepsis. Cell adhesion molecules (E-selectin, VCAM-1, and ICAM-1) were quantified by in-cell ELISA.
Results: Serum and plasma from patients with COVID-19 increased surface expression of cell adhesion molecules. Furthermore, levels of soluble ICAM-1 and E-selectin were elevated in patient serum and tracked 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 restrained upregulation 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 suggest that some patients with COVID-19 have potentially diverse antibodies that drive endotheliopathy, adding important context regarding thrombo-inflammatory effects of autoantibodies in severe COVID-19.