Table 3.
Monitoring of eculizumab therapy and complement activity in atypical hemolytic uremic syndrome (aHUS)
| Mechanism | Recommended levels | Limitations | Advantages | |
|---|---|---|---|---|
| CH50 (total complement activity) | Detects the ability of serum complement to lyse 50% of sheep RBCs in a reaction mixture | <10% of normal | -Normal range depends on the type of assay used -CH50 levels will be low in congenital complement deficiency |
Easy availability |
| AH50 (alternative pathway hemolytic activity) | Tests the ability of alternate or terminal pathway complement components to lyse 50% of rabbit erythrocytes | <10% of normal | -Will be low in congenital deficiency of C3, CFI, CFB, properdin, CFH, and CFD -Normal range depends on the type of assay used |
Easy availability |
| Eculizumab trough levels | ELISA-based assay using C5 coated plates, patient sera, and an anti-human IgG | 50–100 mg/mL | -Assays detect both the bound and unbound fraction43 -Recommended trough levels are based on a meta-analysis of patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with eculizumab33 |
Not affected by complement deficiencies |
| Ex vivo serum-induced endothelial C5b-9 deposits | Patient serum is added to activated endothelial cells and C5b-C9 deposition is assessed | -limited availability79 | ||
| Soluble C5b-C9 levels (sC5b-C9) | Abnormal activation of complement leads to elevated levels of sC5b-C9 and levels should decrease during treatment | Variable results in different studies80,81 | -Longer half-life, detects terminal complement activation as opposed to other markers (C3, C5a) of early complement activity78 |