In vitro C3mRNA Expression in Pemphigus Vulgaris: Complement Activation is Increased by IL-1α and TNF-α

Background: Pemphigus vulgaris (PV) is a potentially life-threatening disease, characterized immunohistologically by IgG deposits and complement activation on the surface of keratinocytes. Complement activation has been implicated in the pathogenesis with C3deposits in about 90% of patients.Objective: In order to further elucidate the role of complement in PV and to define which cytokines play a role in C3mRNA expression, we performed an in vitro study in human keratinocytes.Methods: Normal human epidermal keratinocytes (NHuK) were incubated with PV serum and C3mRNA was measured. We previously had shown that IL-1α and TNF-α are expressed in PV in vivo and in vitro. Since cytokines are able to modulate complement activation, mRNA expression was evaluated in a similar experiment after pretreatment using antibodies against IL-1α and TNF-α.Results: Incubation of NHuK with PV sera caused their detachment from the plates after 20–30 minutes with a complete acantholysis within 12 hours. An early C3mRNA expression was seen after 30 minutes with a peak level after 1 hour. Blocking studies, using antibodies against human IL-1α and TNF-α in NHuK together with PV-IgG, showed reduction of in vitro induced acantholysis and inhibition of C3mRNA expression.Conclusions: This study supports the hypothesis that complement C3is important in PV acantholysis and that complement activation is increased by IL-1α and TNF-α.