Pathogenesis: immunogenetic factors.

The occurrence, albeit infrequent, of systemic vasculitis in closely related family members suggests that both environmental and genetic factors may play a role in the pathogenesis of these diseases. Malfunction of immune regulation in the systemic vasculitides may indicate a role for genes that encode molecules critical to the immune responses. The extremely polymorphic sequences of MHC molecules may provide a structural basis for associations of MHC genes and systemic vasculitis. This review summarizes recent reports of MHC associations, mechanisms by which MHC may play a role in certain vasculitides, and also examines the role for genes encoding non-MHC molecules, such as Fcgamma receptors, cytokines and T cell co-stimulators. Data suggest that the pathogenesis of systemic vasculitides such as giant-cell arteritis, Takayasu's arteritis and Wegener's granulomatosis might be governed by multiple genes encoding host defence molecules, in conjunction with environmental factors.