Inflammatory risk contributes to post-COVID endothelial dysfunction through anti-ACKR1 autoantibody

作者：Ee-Soo Lee, Nhi Nguyen, B. Young, H. Wee, V. Wazny, K. Lee, Kai Yi Tay, L. Goh, F. Chioh, Michelle Cheok Yien Law, I. R. Lee, L. Ang, Kyle M. Loh, Mark Y. Chan, B. Fan, R. Dalan, D. Lye, Laurent Rénia, Christine Cheung · 发表于：Life Science Alliance · 年份：2024 · DOI：10.26508/lsa.202402598 · 被引用次数：4 · 研究领域：Medicine

We study the prevalence and impact of autoantibodies on vascular dysfunction in healthy COVID-19 survivors, revealing elevated anti-ACKR1 autoantibodies associating with systemic cytokines and endothelial dysfunction. Plasma IgG enhances cellular cytotoxicity, suggesting therapeutic avenues to mitigate vascular autoantibody reactivity post-infection. 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 v...