Markers of complement activation, vascular inflammation, endothelial activation and damage, coagulation, and renal injury
| Disease process and biomarker . | Function/association with complement . |
|---|---|
| Complement activation | |
| AP activation | |
| Ba | • Alternative pathway biomarker upstream of C526 |
| • Alternative pathway is stimulated by damaged endothelial cells13 and activated platelets61 | |
| Terminal complement | |
| C5a | • Marker of C5 activation22,23 |
| • Proinflammatory42 | |
| • Mediates chemotaxis, activates endothelial cells, upregulates TNF-α and VCAM-128,41 | |
| Terminal complement | |
| sC5b-9 | • Marker of C5 activation22,23 |
| • Mediates endothelial cell activation,12 glomerular injury,43 and ischemic injury leading to organ damage44 | |
| • Stimulates von Willebrand factor multimer secretion,45 endothelial cell prothrombinase activity,50 and tissue factor expression46 | |
| Vascular inflammation/damage and coagulation | |
| Inflammation | |
| sTNFR1 | • Surrogate, more stable marker for TNF-α27 |
| • TNF-α is pro-inflammatory; associated with vascular49 and chronic renal inflammation and progression of renal failure27,47,48 | |
| • TNF-α upregulated by complement activation51 | |
| Endothelial activation | |
| sVCAM-1 | • Adhesion molecule released by activated endothelial cells29 |
| • Upregulated by TNF-α and terminal complement29,30 | |
| Endothelial cell damage | |
| Thrombomodulin | • Protective against thrombotic risk, inflammation, and complement activation when membrane-bound52 |
| • Released in soluble form by damaged endothelial cells31 | |
| • TNF-α downregulates membrane form and increases release of soluble form32 | |
| Coagulation | |
| Prothrombin fragment F1+2 | • Direct marker of thrombin generation36 |
| • Generated by cleavage of prothrombin after tissue factor–induced coagulation10 | |
| d-dimer | • Fibrin degradation product indicating fibrinolysis37 |
| Renal | |
| Renal injury | |
| Urine cystatin-C | • Proximal tubular injury38,53-55 |
| Clusterin | • Proximal tubular injury38,58,59 |
| β2-microglobulin | • Proximal tubular injury38,60 |
| TIMP-1 | • Interstitial tubular injury40,56 |
| L-FABP-1 | • Deteriorating renal function39,57 |
| Disease process and biomarker . | Function/association with complement . |
|---|---|
| Complement activation | |
| AP activation | |
| Ba | • Alternative pathway biomarker upstream of C526 |
| • Alternative pathway is stimulated by damaged endothelial cells13 and activated platelets61 | |
| Terminal complement | |
| C5a | • Marker of C5 activation22,23 |
| • Proinflammatory42 | |
| • Mediates chemotaxis, activates endothelial cells, upregulates TNF-α and VCAM-128,41 | |
| Terminal complement | |
| sC5b-9 | • Marker of C5 activation22,23 |
| • Mediates endothelial cell activation,12 glomerular injury,43 and ischemic injury leading to organ damage44 | |
| • Stimulates von Willebrand factor multimer secretion,45 endothelial cell prothrombinase activity,50 and tissue factor expression46 | |
| Vascular inflammation/damage and coagulation | |
| Inflammation | |
| sTNFR1 | • Surrogate, more stable marker for TNF-α27 |
| • TNF-α is pro-inflammatory; associated with vascular49 and chronic renal inflammation and progression of renal failure27,47,48 | |
| • TNF-α upregulated by complement activation51 | |
| Endothelial activation | |
| sVCAM-1 | • Adhesion molecule released by activated endothelial cells29 |
| • Upregulated by TNF-α and terminal complement29,30 | |
| Endothelial cell damage | |
| Thrombomodulin | • Protective against thrombotic risk, inflammation, and complement activation when membrane-bound52 |
| • Released in soluble form by damaged endothelial cells31 | |
| • TNF-α downregulates membrane form and increases release of soluble form32 | |
| Coagulation | |
| Prothrombin fragment F1+2 | • Direct marker of thrombin generation36 |
| • Generated by cleavage of prothrombin after tissue factor–induced coagulation10 | |
| d-dimer | • Fibrin degradation product indicating fibrinolysis37 |
| Renal | |
| Renal injury | |
| Urine cystatin-C | • Proximal tubular injury38,53-55 |
| Clusterin | • Proximal tubular injury38,58,59 |
| β2-microglobulin | • Proximal tubular injury38,60 |
| TIMP-1 | • Interstitial tubular injury40,56 |
| L-FABP-1 | • Deteriorating renal function39,57 |