Silicates and Autoimmunity

Inhalation of particulate matter is associated with a number of acute and chronic disorders including autoimmune rheumatic diseases. The strongest evidence for a link with autoimmune disease comes from epidemiological studies describing the association of occupational exposure to crystalline silica dust with the systemic autoimmune diseases SLE and RA. Very little is known regarding the mechanism by which silica exposure leads to systemic autoimmune disease. However, in the case of silicosis, there is an extensive research literature that can help identify disease processes that may precede development of autoimmunity. The pathophysiology of silicosis consists of deposition of particles into the alveoli of the lung where they cannot be cleared. Ingestion of deposited particles by alveolar macrophages initiates an inflammatory response which then stimulates fibroblasts to proliferate and produce collagen. Silica particles are enveloped by collagen leading to fibrosis and nodular lesions. These findings are consistent with an autoimmune pathogenesis that begins with activation of the innate immune system leading to proinflammatory cytokine production, inflammation of the lung leading to activation of adaptive immunity, breaking of tolerance, autoantibodies, and tissue damage. The variable frequency of these features following silica exposure suggests significant genetic involvement and gene/environment interaction in silica-induced autoimmunity.