Review
Copyright ©The Author(s) 2018.
World J Transplantation. Sep 10, 2018; 8(5): 122-141
Published online Sep 10, 2018. doi: 10.5500/wjt.v8.i5.122
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 troughMay 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 assaysThe 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.