Sarcoidosis: genes and microbes--soil or seed?

Sarcoidosis is a multi-organ granulomatous disorder that is characterised by the accumulation of CD4+ T-lymphocytes resulting in a Th-1 type immune response. Although our understanding of the immune response in sarcoidosis has improved in recent years through studies of bronchoalveolar lavage cells and fluid, the genetic predisposition and trigger factors (and their interrelationship) remain unclear. Previous reports of familial clustering and varying prevalence of sarcoidosis in different populations suggested molecular epidemiological heterogeneity. This review focuses specifically on two pivotal areas that have been the subjects of intensive investigation recently: a) triggering by infective agents and b) host genetic susceptibility and relates these to broader issues of pathogenesis. It is concluded that one or more microbes behaving in a non-infectious fashion in a genetically predisposed individual trigger the sarcoidosis granulomatous response.