Genes, hormones, immunosenescence, and environmental agents: Toward an integrated view of the genesis of autoimmune disease

Abstract

Autoimmune diseases, a group of dozens of distinct disorders that target every organ system, affect as much as 10 % of the US population and are increasing in prevalence worldwide. The mechanisms which underlie these diverse diseases are not understood. Autoimmune disease has a strong genetic component, and nearly 80 % of its victims are women, suggesting a strong hormonal contribution. Environmental agents (e.g., lupus-like syndromes induced by pharmaceuticals) can also be a factor. Since the risk of autoimmune disease and levels of circulating antibodies rise with age, a progressive deterioration of the immune system (termed immunosenescence) is implicated. As data on the origin of autoimmune disease begin to come together from diverse disciplines, it is becoming clear that a set of shared proteins common to several immune pathways are involved in multiple diseases and that the respective contributions from genetics, sex hormones, environmental insults, and immunosenescence are put in play by epigenetic mechanisms that control gene expression. Since those changes are reversible, epigenetics presents a promising new approach for autoimmune disease therapies.