It is intriguing that spontaneous complement activation in vitro, a condition that may mimic the chronic low level of complement activation present in vivo, results in the same order of C3 binding we have previously observed in vivo in PNH patients (n = 41) on eculizumab: 29 vs. 27% [23]. Here, C3 is linked to paroxysmal nocturnal hemoglobinuria.