Summary of Nilsson, P. et al; Eculuzimab-C5 complexes express a C5a neoepitope in vivo: Consequences for interpretation of patient complement analyses. ScienceDirect 2017. Click here for the full article.
The complement system has obtained renewed clinical focus due to an increasing number of patients treated with eculizumab, a monoclonal antibody inhibiting cleavage of C5 into C5a and C5b for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).
 
This study identifies the expression of a neoepitope which was exposed on C5 after binding to eculizumab in vivo. This finding is important to evaluate whether complement inhibitory treatment is indicated and if treatment is effective. Serum was collected from 22 individuals ranging from healthy subjects to patients with genetic C5-deficiency or antiphospholipid syndrome. C5a was monitored for the diseased individuals before and after administration of eculizumab by using the Hycult Biotech C5a ELISA (HK349) and the BD C5a kit.

The results showed that the administration of eculizumab induced a false-positive c5a signal in plasma detected with BD C5a ELISA kit which was not observed in the Hycult Biotech assay. This is caused by the expression of a neoepitope which was exposed on C5 after binding to eculizumab in vivo. These data are important for interpretation of complement analyses in patients treated with eculizumab and confirms that assays used for quantification of C5a should be carefully checked for reactivity against C5 bound to eculizumab.