Sarcoidosis: A Model of Granulomatous Inflammation of Unknown Etiology Associated with a Hyperactive Immune System

Sarcoidosis is a systemic granulomatous disorder of unknown etiology, characterized by hyperactive cellular and humoral immune function. We review pertinent history, pathology, and biochemistry of sarcoidosis and reconcile the common finding of cutaneous anergy with the presence of a hyperactive immune system. A hypothetical model of antigen-driven granuloma formation is discussed, citing relevant studies from blood, bronchoalveolar lavage, and in vitro-cultured intact sarcoidal skin granulomas. The etiology of sarcoidosis is considered, and we focus on the Kveim-Siltzbach skin test as an in vivo model for elucidation of the immune mechanisms of sarcoid granuloma formation, as well as a model for study of the sarcoid granulomagenic factor. We have adapted this skin test model to study the granulomagenicity of sarcoid autologous bronchoalveolar lavage and peripheral blood cells and demonstrate that early after onset of disease symptoms, bronchoalveolar lavage macrophages and peripheral blood monocytes are granulomagenic. This method extends our understanding of the source of the sarcoid granulomagenic factor and offers a model for tracking the agent as its identity is unraveled.