tetano
Editor, Senior Moderator
Clin Immunol Commun
. 2022 Dec:2:83-90.
doi: 10.1016/j.clicom.2022.05.001. Epub 2022 May 5. C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?
Melissa A Hausburg[SUP] 1 2 3 [/SUP], Jason S Williams[SUP] 1 2 3 [/SUP], Kaysie L Banton[SUP] 1 [/SUP], Charles W Mains[SUP] 4 [/SUP], Michael Roshon[SUP] 4 5 [/SUP], David Bar-Or[SUP] 1 2 3 6 [/SUP]
Affiliations
From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement activation and FXIIa, C1 esterase inhibitor (C1-INH), is increased in COVID-19 patient plasma and is associated with disease severity. Here we review the role of C1-INH in the regulation of innate and adaptive immune responses. Additionally, we contextualize regulation of C1-INH and SERPING1, the gene encoding C1-INH, by other pathogens and SARS viruses and propose that viral proteins bind to C1-INH to inhibit its function in severe COVID-19. Finally, we review the current clinical trials and published results of exogenous C1-INH treatment in COVID-19 patients.
Keywords: C1 esterase inhibitor; C1 esterase inhibitor, C1-INH; C1-INH; COVID-19; Complement; FXII; Inflammation; Middle East respiratory syndrome coronavirus, MERS-CoV; Mycobacterium tuberculosis, Mtb; Severe acute respiratory syndrome coronavirus, SARS-CoV; acquired C1-INH deficiency, AEE; activated plasma kallikrein, PKa; antibody-mediated rejection, AMR; bradykinin, BK; contact system, CS; coronavirus disease 2019, COVID-19; exogenous C1-INH, exC1-INH; hereditary angioedema, HAE; high-molecular-weight kininogen, HK; human immunodeficiency virus, HIV; interferon, IFN; interleukin, IL; ischemia/reperfusion injury, IRI; mannose-binding lectin, MBL; prekallikrein, PK; recombinant C1-INH, rhC1-INH; serine protease inhibitor, serpin; tuberculosis, TB
. 2022 Dec:2:83-90.
doi: 10.1016/j.clicom.2022.05.001. Epub 2022 May 5. C1 esterase inhibitor-mediated immunosuppression in COVID-19: Friend or foe?
Melissa A Hausburg[SUP] 1 2 3 [/SUP], Jason S Williams[SUP] 1 2 3 [/SUP], Kaysie L Banton[SUP] 1 [/SUP], Charles W Mains[SUP] 4 [/SUP], Michael Roshon[SUP] 4 5 [/SUP], David Bar-Or[SUP] 1 2 3 6 [/SUP]
Affiliations
- PMID: 38013973
- PMCID: PMC9068237
- DOI: 10.1016/j.clicom.2022.05.001
From asymptomatic to severe, SARS-CoV-2, causative agent of COVID-19, elicits varying disease severities. Moreover, understanding innate and adaptive immune responses to SARS-CoV-2 is imperative since variants such as Omicron negatively impact adaptive antibody neutralization. Severe COVID-19 is, in part, associated with aberrant activation of complement and Factor XII (FXIIa), initiator of contact system activation. Paradoxically, a protein that inhibits the three known pathways of complement activation and FXIIa, C1 esterase inhibitor (C1-INH), is increased in COVID-19 patient plasma and is associated with disease severity. Here we review the role of C1-INH in the regulation of innate and adaptive immune responses. Additionally, we contextualize regulation of C1-INH and SERPING1, the gene encoding C1-INH, by other pathogens and SARS viruses and propose that viral proteins bind to C1-INH to inhibit its function in severe COVID-19. Finally, we review the current clinical trials and published results of exogenous C1-INH treatment in COVID-19 patients.
Keywords: C1 esterase inhibitor; C1 esterase inhibitor, C1-INH; C1-INH; COVID-19; Complement; FXII; Inflammation; Middle East respiratory syndrome coronavirus, MERS-CoV; Mycobacterium tuberculosis, Mtb; Severe acute respiratory syndrome coronavirus, SARS-CoV; acquired C1-INH deficiency, AEE; activated plasma kallikrein, PKa; antibody-mediated rejection, AMR; bradykinin, BK; contact system, CS; coronavirus disease 2019, COVID-19; exogenous C1-INH, exC1-INH; hereditary angioedema, HAE; high-molecular-weight kininogen, HK; human immunodeficiency virus, HIV; interferon, IFN; interleukin, IL; ischemia/reperfusion injury, IRI; mannose-binding lectin, MBL; prekallikrein, PK; recombinant C1-INH, rhC1-INH; serine protease inhibitor, serpin; tuberculosis, TB