Journal: Journal of Clinical Medicine

Article Title: Targeting the Complement Cascade in the Pathophysiology of COVID-19 Disease

doi: 10.3390/jcm10102188

Figure Lengend Snippet: Complement activation pathways. The classical pathway is activated by the binding of antibody-antigen complex with the C1 esterase complex (C1qC1rC1s), which then forms C3 convertase (C4b2a). The lectin pathway is initiated by the binding of mannose-binding lectin with mannose residues on pathogen surfaces, which activates mannose-associated serine proteases (MASPs) to form the same C3 convertase (C4b2a). The alternative pathway is triggered directly by antigen and also through spontaneous autoactivation, leading to the formation of a similar C3 convertase (C3bBb). These C3 convertases hydrolyze C3 to yield the C5 convertases (C4b2a3b and C3bBbC3b, respectively), which culminates in the generation of C5b-9 or MAC (membrane attack complex).

Article Snippet: Across multiple studies by Cugno et al., de Nooijer et al., Holter et al., and Peffault de Latour et al., complement factors and soluble terminal complement complex (sC5b-9 or sMAC) levels were associated with either increased odds of respiratory failure, need for oxygen therapy, and/or more severe disease [ , , , ].

Techniques: Activation Assay, Binding Assay, Membrane

Journal: Journal of Clinical Medicine

Article Title: Targeting the Complement Cascade in the Pathophysiology of COVID-19 Disease

doi: 10.3390/jcm10102188

Figure Lengend Snippet: Integration between the complement and coagulation cascades. Relationship between the complement and coagulation cascades, as well as platelet activation is highlighted. Most notable are the effects of MASPs on thrombin, factor XIIIa, and fibrinogen; C5a on tissue factor; and C5b-9 on thrombin. Adapted from Hill et al. .

Article Snippet: Across multiple studies by Cugno et al., de Nooijer et al., Holter et al., and Peffault de Latour et al., complement factors and soluble terminal complement complex (sC5b-9 or sMAC) levels were associated with either increased odds of respiratory failure, need for oxygen therapy, and/or more severe disease [ , , , ].

Techniques: Coagulation, Activation Assay

Journal: Journal of Clinical Medicine

Article Title: Targeting the Complement Cascade in the Pathophysiology of COVID-19 Disease

doi: 10.3390/jcm10102188

Figure Lengend Snippet: Therapeutic targets in the complement cascade for the treatment of coronavirus disease 2019 (COVID-19) pneumonia.

Article Snippet: Across multiple studies by Cugno et al., de Nooijer et al., Holter et al., and Peffault de Latour et al., complement factors and soluble terminal complement complex (sC5b-9 or sMAC) levels were associated with either increased odds of respiratory failure, need for oxygen therapy, and/or more severe disease [ , , , ].

Techniques: Biomarker Discovery

Journal: Clinical and Experimental Immunology

Article Title: Plasma levels of soluble membrane attack complex are elevated despite viral suppression in HIV patients with poor immune reconstitution

doi: 10.1111/cei.13366

Figure Lengend Snippet: Soluble membrane attack complex of complement (sMAC) levels in plasma and serum in healthy adults. Plasma and serum samples from healthy donor cohorts were examined for sMAC levels using the Quidel SC5b‐9 enzyme‐linked immunosorbent assay (ELISA). (a) sMAC levels in plasma (n = 199) and serum (n = 49) from healthy adults. sMAC levels were lower in plasma than in serum (121·8 ± 2·7 ng/ml versus 175·3 ± 8·1 ng/ml, respectively, P < 0·0001, unpaired Student’s t‐test). (b) Plasma sMAC levels between male (n = 118) and female (n = 81) donors were not significantly different (P = 0·37, unpaired Student’s t‐test). (c) Plasma sMAC levels in African Americans (n = 24) were not significantly higher than in Caucasians (n = 170) (137·8 ± 7·8 ng/ml versus 119·5 ± 2·9 ng/ml; F‐test, P = 0·89). (d) Plasma sMAC levels increase with age. sMAC levels were significantly lower in young (30–39 years) versus older adults (50–69 years); P < 0·0028, one‐way analysis of variance (ANOVA). *P = 0·01.

Article Snippet: Plasma and serum samples from healthy donor cohorts were examined for sMAC levels using the Quidel SC5b‐9 enzyme‐linked immunosorbent assay (ELISA). (a) sMAC levels in plasma ( n = 199) and serum ( n = 49) from healthy adults. sMAC levels were lower in plasma than in serum (121·8 ± 2·7 ng/ml versus 175·3 ± 8·1 ng/ml, respectively, P < 0·0001, unpaired Student’s t ‐test). (b) Plasma sMAC levels between male ( n = 118) and female ( n = 81) donors were not significantly different ( P = 0·37, unpaired Student’s t ‐test). (c) Plasma sMAC levels in African Americans ( n = 24) were not significantly higher than in Caucasians ( n = 170) (137·8 ± 7·8 ng/ml versus 119·5 ± 2·9 ng/ml; F ‐test, P = 0·89). (d) Plasma sMAC levels increase with age. sMAC levels were significantly lower in young (30–39 years) versus older adults (50–69 years); P < 0·0028, one‐way analysis of variance (ANOVA).

Techniques: Enzyme-linked Immunosorbent Assay