tetano
Editor, Senior Moderator
J Biomed Sci
. 2024 Apr 18;31(1):39.
doi: 10.1186/s12929-024-01026-5. Enhancement of NETosis by ACE2-cross-reactive anti-SARS-CoV-2 RBD antibodies in patients with COVID-19
Kun-Han Hsieh[SUP] #[/SUP][SUP] 1 [/SUP], Chiao-Hsuan Chao[SUP] #[/SUP][SUP] 1 2 [/SUP], Yi-Ling Cheng[SUP] 1 [/SUP], Yen-Chung Lai[SUP] 3 4 [/SUP], Yung-Chun Chuang[SUP] 1 5 6 [/SUP], Jen-Ren Wang[SUP] 1 7 8 [/SUP], Sui-Yuan Chang[SUP] 9 10 [/SUP], Yuan-Pin Hung[SUP] 11 12 [/SUP], Yi-Ming Arthur Chen[SUP] 13 14 15 [/SUP], Wei-Lun Liu[SUP] 14 16 17 [/SUP], Woei-Jer Chuang[SUP] 18 [/SUP], Trai-Ming Yeh[SUP] 19 20 [/SUP]
Affiliations
Background: High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown.
Methods: In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied.
Results: An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection.
Conclusions: Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients.
Keywords: Anti-ACE2 autoantibody; COVID-19; Cross-reactivity; NETosis; Thrombosis.
. 2024 Apr 18;31(1):39.
doi: 10.1186/s12929-024-01026-5. Enhancement of NETosis by ACE2-cross-reactive anti-SARS-CoV-2 RBD antibodies in patients with COVID-19
Kun-Han Hsieh[SUP] #[/SUP][SUP] 1 [/SUP], Chiao-Hsuan Chao[SUP] #[/SUP][SUP] 1 2 [/SUP], Yi-Ling Cheng[SUP] 1 [/SUP], Yen-Chung Lai[SUP] 3 4 [/SUP], Yung-Chun Chuang[SUP] 1 5 6 [/SUP], Jen-Ren Wang[SUP] 1 7 8 [/SUP], Sui-Yuan Chang[SUP] 9 10 [/SUP], Yuan-Pin Hung[SUP] 11 12 [/SUP], Yi-Ming Arthur Chen[SUP] 13 14 15 [/SUP], Wei-Lun Liu[SUP] 14 16 17 [/SUP], Woei-Jer Chuang[SUP] 18 [/SUP], Trai-Ming Yeh[SUP] 19 20 [/SUP]
Affiliations
- PMID: 38637878
- DOI: 10.1186/s12929-024-01026-5
Background: High levels of neutrophil extracellular trap (NET) formation or NETosis and autoantibodies are related to poor prognosis and disease severity of COVID-19 patients. Human angiotensin-converting enzyme 2 (ACE2) cross-reactive anti-severe acute respiratory syndrome coronavirus 2 spike protein receptor-binding domain (SARS-CoV-2 RBD) antibodies (CR Abs) have been reported as one of the sources of anti-ACE2 autoantibodies. However, the pathological implications of CR Abs in NET formation remain unknown.
Methods: In this study, we first assessed the presence of CR Abs in the sera of COVID-19 patients with different severity by serological analysis. Sera and purified IgG from CR Abs positive COVID-19 patients as well as a mouse monoclonal Ab (mAb 127) that can recognize both ACE2 and the RBD were tested for their influence on NETosis and the possible mechanisms involved were studied.
Results: An association between CR Abs levels and the severity of COVID-19 in 120 patients was found. The CR Abs-positive sera and IgG from severe COVID-19 patients and mAb 127 significantly activated human leukocytes and triggered NETosis, in the presence of RBD. This NETosis, triggered by the coexistence of CR Abs and RBD, activated thrombus-related cells but was abolished when the interaction between CR Abs and ACE2 or Fc receptors was disrupted. We also revealed that CR Abs-induced NETosis was suppressed in the presence of recombinant ACE2 or the Src family kinase inhibitor, dasatinib. Furthermore, we found that COVID-19 vaccination not only reduced COVID-19 severity but also prevented the production of CR Abs after SARS-CoV-2 infection.
Conclusions: Our findings provide possible pathogenic effects of CR Abs in exacerbating COVID-19 by enhancing NETosis, highlighting ACE2 and dasatinib as potential treatments, and supporting the benefit of vaccination in reducing disease severity and CR Abs production in COVID-19 patients.
Keywords: Anti-ACE2 autoantibody; COVID-19; Cross-reactivity; NETosis; Thrombosis.