Alternative complement pathway hemolytic assays reveal incomplete complement blockade in patients treated with eculizumab
2017
Abstract
Eculizumabis a monoclonal anti-C5 antibody used in the treatment of
atypical hemolytic uremic syndrome(aHUS). We monitored complement inhibition in 16
eculizumab-treated patients suffering from HUS or
transplant rejection(not aHUS patients). Blood samples were obtained one to four weeks after the last
eculizumabinjection. We observed that
eculizumabefficiently blocked the terminal pathway (TP) through classical pathway (CP) activation measured by kinetic hemolytic assay (HA) ( 23%) or chicken erythrocytes HA (AP100 > 15%). Conversely, functional ELISA revealed a complete blockade of TP through AP activation in all patients ( Similar results were obtained after in vitro addition of increasing amounts of
eculizumabto a control serum ( in vitro APH50 > 60% and AP100 > 20%). We also showed that ELISA was less sensitive than HA.
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