Fig. 4.

CDC and ADCC by anti-TNF agents.

Infliximab, adalimumab and etanercept commonly possess the Fc portion of IgG1, whose CH2 domain activates complement C1. Activation of C1 leads to complement C3 activation and subsequent formation of a membrane attack complex (C5b–C9) and lysis of the target cells. However, etanercept does not carry the CH1 domain of IgG1 which is important for the activation of C3. Infliximab, adalimumab and etanercept carry CH2 and CH3 domains of the Fc domain of IgG1 that mediate the binding to Fc receptors, which culminates in granzyme B and perforin release from NK cells and lysis of the target cells.