tetano
Editor, Senior Moderator
Life Sci Alliance
. 2024 May 13;7(7):e202402598.
doi: 10.26508/lsa.202402598. Print 2024 Jul. Inflammatory risk contributes to post-COVID endothelial dysfunction through anti-ACKR1 autoantibody
Ee-Soo Lee[SUP] 1 [/SUP], Nhi Nguyen[SUP] 1 [/SUP], Barnaby E Young[SUP] 1 2 3 4 [/SUP], Hannah Wee[SUP] 1 [/SUP], Vanessa Wazny[SUP] 1 [/SUP], Khang Leng Lee[SUP] 1 [/SUP], Kai Yi Tay[SUP] 1 [/SUP], Liuh Ling Goh[SUP] 5 [/SUP], Florence Wj Chioh[SUP] 1 [/SUP], Michelle Cy Law[SUP] 1 [/SUP], I Russel Lee[SUP] 4 [/SUP], Lay Teng Ang[SUP] 6 [/SUP], Kyle M Loh[SUP] 6 7 [/SUP], Mark Y Chan[SUP] 2 8 [/SUP], Bingwen E Fan[SUP] 1 2 9 10 [/SUP], Rinkoo Dalan[SUP] 1 2 5 [/SUP], David C Lye[SUP] 1 2 3 4 [/SUP], Laurent Renia[SUP] 1 11 [/SUP], Christine Cheung[SUP] 12 13 [/SUP]
Affiliations
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.
. 2024 May 13;7(7):e202402598.
doi: 10.26508/lsa.202402598. Print 2024 Jul. Inflammatory risk contributes to post-COVID endothelial dysfunction through anti-ACKR1 autoantibody
Ee-Soo Lee[SUP] 1 [/SUP], Nhi Nguyen[SUP] 1 [/SUP], Barnaby E Young[SUP] 1 2 3 4 [/SUP], Hannah Wee[SUP] 1 [/SUP], Vanessa Wazny[SUP] 1 [/SUP], Khang Leng Lee[SUP] 1 [/SUP], Kai Yi Tay[SUP] 1 [/SUP], Liuh Ling Goh[SUP] 5 [/SUP], Florence Wj Chioh[SUP] 1 [/SUP], Michelle Cy Law[SUP] 1 [/SUP], I Russel Lee[SUP] 4 [/SUP], Lay Teng Ang[SUP] 6 [/SUP], Kyle M Loh[SUP] 6 7 [/SUP], Mark Y Chan[SUP] 2 8 [/SUP], Bingwen E Fan[SUP] 1 2 9 10 [/SUP], Rinkoo Dalan[SUP] 1 2 5 [/SUP], David C Lye[SUP] 1 2 3 4 [/SUP], Laurent Renia[SUP] 1 11 [/SUP], Christine Cheung[SUP] 12 13 [/SUP]
Affiliations
- PMID: 38740432
- DOI: 10.26508/lsa.202402598
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.