Environment and autoimmune disease: an ongoing dilemma
Scientific papers, newly published in the Journal of Autoimmunity, were inspired by the September 2010 workshop sponsored by the National Institute of Environmental Health Sciences (NIEHS). The papers have as their common goal the improvement of diagnosis, treatment, and prevention of autoimmune disease in the future. "As autoimmune diseases become increasingly prevalent, the urgency to meet these goals grows," commented NIEHS Division of Extramural Research and Training program administrator Mike Humble, Ph.D.
• In "Criteria for environmentally associated autoimmune diseases," by Frederick Miller, M.D., Ph.D., et al., the authors indicate that an important unresolved issue is the development of criteria for identifying autoimmune disease phenotypes, i.e., the genetically and environmentally determined physical appearance of the organisms involved.
Dr. Miller and fellow authors say that current studies suggest that multiple lines of complementary evidence will be important. They suggest, for example, clinical, serologic [serum], genetic, epigenetic [utilizing cells as building units], and/or other laboratory features that could be incorporated. These could be incorporated as criteria for environmentally associated autoimmune diseases not only to improve diagnosis and treatment but also to possibly allow for preventative strategies in the future.
• In "Mechanisms of environmental influence on human autoimmunity: A national institute of environmental health sciences expert panel workshop," Carlo Selmi, M.D., et al., state, "The growing number of genome-wide association studies and the largely incomplete concordance for autoimmune diseases in monozygotic [identical] twins support the role of the environment (including infectious agents and chemicals) in the breakdown of tolerance leading to autoimmunity via numerous mechanisms."
The authors say that the working hypotheses which they propose, such as, epigenetic changes, particularly DNA methylation, that are induced by environmental stimuli and may contribute to autoimmune initiation, "should be viewed in parallel with animal models and epidemiological observations to provide a comprehensive picture of the environmental causes of autoimmune diseases."
• In "Epidemiology of environmental exposures and human autoimmune diseases: Findings from a National Institute of Environmental Health Sciences Expert Panel Workshop," Frederick Miller, M.D., Ph.D., et al., summarize the state of knowledge and their levels of confidence in the role of specific agents in the development of autoimmune diseases; and they define the areas which they feel are of greatest impact for future investigations. These are crystalline silica exposure (several autoimmune diseases), solvent exposure (systemic sclerosis), smoking (seropositive rheumatoid arthritis), and an inverse association between ultraviolet radiation and the risk of multiple sclerosis.
Dr. Miller and the authors suggest that some knowledge gaps needing investigation include defining important windows in the timing of exposures and latencies relating to age, developmental state, and hormonal changes; understanding dose-response relationships; and clarifying mechanisms for disease development. The authors state that "knowledge of the risks conferred by environmental factors in specific genetic contexts could pave the way for prevention of autoimmune diseases in the future."
• In "Animal models used to examine the role of the environment in the development of autoimmune disease: Findings from an NIEHS Expert Panel Workshop," Dori Germolec, Ph.D., Head of the NIEHS Division of the National Toxicology Program Systems Toxicology Group (NTP), and fellow authors say that human studies are extremely limited in their ability to test isolated exposures to environmental factors in order to demonstrate causation or to assess pathogenic mechanisms.
An objective of Dr. Germolec and the authors was to assess the types of information that can be gleaned from the use of animal models and how well that information can be used to translate back to human health. Their review notes the importance of genetic background to the types and severity of the autoimmune response following exposure to environmental factors, and it emphasizes literature where animal model studies have led to increased confidence about environment factors that affect expression of autoimmunity.
--Sources: "NIEHS workshop inspires new papers on autoimmunity," Cindy Loose, NIEHS Environmental Factor, September 2012; and abstracts as listed in article, Journal of Autoimmunity, June 25, 27, 28, 2012; and July 5, 2012. Photos courtesy of Steve McCaw.
