Chapter 20 - Noninfectious Environmental Agents and Autoimmunity

Abstract

Autoimmune diseases appear to be increasing throughout the world, yet their rarity, heterogeneity and complex etiologies have limited our understanding of their pathogeneses. While the precise mechanisms for the development of autoimmune diseases are not known, evidence from many complementary lines of research suggests that autoimmune diseases result from the interactions of both environmental and genetic risk factors, in the context of the relative absence of protective factors. Considerable progress has been made in understanding the multiple and sometimes shared genetic risk factors for many autoimmune diseases, however, relatively little information has been collected regarding the role of the environment in the development of these illnesses. Here we examine the challenges in defining environmental risk and protective factors for disease, the limited but growing evidence for the role of noninfectious environmental exposures in the development and progression of autoimmune diseases, the specific exposures that have been suspected of being involved, the possible mechanisms by which these agents may induce and sustain autoimmune processes, and the approaches needed to better understand these issues in the future. Identifying the necessary and sufficient genetic and environmental risk and protective factors for disease phenotypes may eventually allow for the prevention of some illnesses. This could be accomplished through avoidance of environmental risk factors or by enhancing exposure to protective factors in genetically susceptible individuals, or via gene or other therapies to correct the effects of deleterious genetic risk factors in the case of unavoidable environmental risk agents. More efforts need to be dedicated to identify such risk and protective factors given the clinical and financial importance of the prevention of autoimmune disease in the future.