Table 6.

Monitoring eculizumab therapy

Description
CH50 (total complement activity)	Measures the combined activity of all of the complement pathways Tests the functional capability of serum complement components to lyse 50% of sheep erythrocytes in a reaction mixture Low in congenital complement deficiency (C1-8) or during complement blockade Normal range is assay dependent Recommended goal during therapeutic complement blockade: < 10% of normal
AH50 (alternative pathway hemolytic activity)	Measures combined activity of alternative and terminal complement pathways Tests the functional capability of alternate or terminal pathway complement components to lyse 50% of rabbit erythrocytes in a Mg2+-EGTA buffer Will be low in congenital C3, FI, FB, properdin, FH, and FD deficiencies or during terminal complement blockade Normal range is assay dependent Recommended goal during complement blockade: < 10% of normal
Eculizumab trough	May be a free or bound level ELISA: Using C5 coated plates, patient sera, and an anti-human IgG detection system Not affected by complement deficiencies Recommended trough level during complement blockade: 50-100 μg/mL
Alternative assays	The following assays are under investigation (or awaiting to be replicated in different laboratories)[83] as a means to monitor therapeutic complement blockade Free C5 In vitro human microvascular endothelial cell test sC5b -9 (also referred to as sMAC and TCC) may remain detectable in aHUS patients in remission and therefore is not recommended as a monitoring tool

Adapted from: Goodship et al[58]. aHUS: Atypical hemolytic uremic syndrome; C3: Complement component 3; C5: Complement component 5; EGTA: Ethyleneglycol tetraacetic acid; ELISA: Enzyme-linked immunosorbent assay; FB: Complement factor B; FD: Complement factor D; FH: Complement factor H; FI: Complement factor I; sC5b-9: Soluble C5b-9; sMAC: Soluble membrane attack complex; TCC: Terminal complement complex.