Inflammatory risk contributes to post-COVID endothelial dysfunction through anti-ACKR1 autoantibody.
Life Sci Alliance
; 7(7)2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38740432
ABSTRACT
Subclinical vascular impairment can be exacerbated in individuals who experience sustained inflammation after COVID-19 infection. Our study explores the prevalence and impact of autoantibodies on vascular dysfunction in healthy COVID-19 survivors, an area that remains inadequately investigated. Focusing on autoantibodies against the atypical chemokine receptor 1 (ACKR1), COVID-19 survivors demonstrated significantly elevated anti-ACKR1 autoantibodies, correlating with systemic cytokines, circulating damaged endothelial cells, and endothelial dysfunction. An independent cohort linked these autoantibodies to increased vascular disease outcomes during a median 6.7-yr follow-up. We analyzed a single-cell transcriptome atlas of endothelial cells from diverse mouse tissues, identifying enriched Ackr1 expressions in venous regions of the brain and soleus muscle vasculatures, which holds intriguing implications for tissue-specific venous thromboembolism manifestations reported in COVID-19. Functionally, purified immunoglobulin G (IgG) extracted from patient plasma did not trigger cell apoptosis or increase barrier permeability in human vein endothelial cells. Instead, plasma IgG enhanced antibody-dependent cellular cytotoxicity mediated by patient PBMCs, a phenomenon alleviated by blocking peptide or liposome ACKR1 recombinant protein. The blocking peptide uncovered that purified IgG from COVID-19 survivors possessed potential epitopes in the N-terminal extracellular domain of ACKR1, which effectively averted antibody-dependent cellular cytotoxicity. Our findings offer insights into therapeutic development to mitigate autoantibody reactivity in blood vessels in chronic inflammation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autoanticorpos
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SARS-CoV-2
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COVID-19
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Life Sci Alliance
/
Life sci. alliance
/
Life science alliance
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Singapura