Environmental exposure autoimmunity

Ravel G, Christ M, Howard F, Descotes J. Autoimmunity, environmental exposure and vaccination Is there a link Toxicology. 2004 196 211-216. 

Autoimmunity, Autoimmune Diseases and the Role of Environmental Exposures... 

Summary of Research on Specific Environmental Exposures and Autoimmune Diseases... 

The causal relationship between environmental exposure and autoimmune disease onset is seen from the data derived from studies of monozygotic twins. The concordance of autoimmune disease among such twins is only in the 25-40% range, low enough to implicate environmental exposure, yet high enough to indicate genetic influences as well)33... 

Van Loveren H, Vox JG, Germolec D, et al. Epidemiological associations between occupational and environmental exposures and autoimmune disease Report of a meeting to explore current evidence and identify research needs. Int JHygEnviron Health 2001 203(5-6) 483-95. 

Type 1 DM is characterized by an absolute deficiency of insulin. Most often this is the result of an immune-mediated destruction of pancreatic p cells, but rare unknown or idiopathic processes may contribute. What is evident are four main features (1) a long preclinical period marked by the presence of immune markers when /3-cell destruction is thought to occur (2) hyperglycemia when 80% to 90% of p cells are destroyed (3) transient remission (the so-called, honeymoon phase) and (4) established disease with associated risks for complications and death. Unknown is whether there is one or more inciting factors (e.g., cow s milk, or viral, dietary, or other environmental exposure) that initiate the autoimmune process (Fig. 72-4). 

There exist a variety of methods to detect enhanced antibody formation and autoantibodies in humans and experimental animals following environmental exposure. In contrast, tests available for measuring the potential of chemicals or environmental factors to produce autoimmune disease or augment existing autoimmune disease are not readily available. 

The heterogeneity of most of the systemic but also organ-specific autoimmune diseases is an additional important factor that complicates genetic analyses. Careful disease classification is necessary, and differentiation of subgroups according to clinical presentation, autoantibody production, ethnic background, as well as environmental exposures may be helpful. The risk associated with one genetic risk factor for an autoimmune disease may be... 

Studies of autoantibodies in the general population allow us to determine the prevalence of specific autoantibodies among people who do not have a clinically evident autoimmune disease, whether the prevalence of autoantibodies reflects the demographic variation in disease risk and whether specific environmental exposures are related to the expression of specific autoantibodies. These studies are most feasible for the autoantibodies associated with the most common autoimmune diseases diabetes mellitus type 1, autoimmune thyroid disease, and rheumatoid arthritis. Important issues with respect to interpreting these types of studies include the type of test used and definition of a positive result. 

Although a number of studies have demonstrated that various metals may play a primary role in mediating PM-related cardiopulmonary health effects and autoimmunity, less is known regarding the potential impacts of environmental exposures to PGE. In particular, very httle data is available regarding the sub-clinical effects of chronic low dose exposures. This is especially relevant regarding attempts to assess the effects of exposures to low concentrations of PGE that are being continuously emitted into the environment. 

Immunoenhancement, which, as adverse effect, may lead to immune-mediated diseases such as hypersensitivity reactions and autoimmune diseases. Hypersensitivity reactions are the result of normally beneficial immune responses acting inappropriately, causing inflammatory reactions and tissue damage. The two most frequent manifestation of chemical-induced allergy are contact hypersensitivity and respiratory sensitization, both of which can have a serious impact on quality of life and represent a common occupational health problem. Hypersensitivity reactions are often considered to be increased at such a rate to become a major health problem in relation to environmental chemical exposure. 

For some autoimmune diseases, little is known about environmental factors involved in the initiation or progression of the disease. For other diseases, however, considerable research has been conducted on one or more types of exposures. Most epidemiologic studies of environmental influences have focused on multiple sclerosis, rheumatoid arthritis, scleroderma, systemic lupus erythematosus, and small vessel vasculitis, but experimental studies using murine models of these diseases is limited (Table 25.1). 

This chapter reviewed current research pertaining to selected environmental agents and autoimmune diseases (Table 25.3). Other infectious agents (e.g., parvovirus, varicella), occupational exposures (e.g., mercury), dietary factors (dietary supplements, nutrients such as antioxidants, and specific proteins in wheat and other grains implicated in celiac disease), and stress have been the focus of additional research that was not included in this review. 

Blossom, S.J., Pumford, N.R., and Gilbert, K.M., Activation and attenuation of apoptosis of CD4+ T cells following in vivo exposure to two common environmental toxicants, trichloroacetaldehyde hydrate and trichloroacetic acid, J. Autoimmun., 23, 211, 2004. 

WHO (2006) International Programme on Chemical Safety, Principles and methods for assessing autoimmunity associated with exposure to chemicals. Environmental Health Criteria 236, WHO, Geneva, Zwitserland. 

Environmental factors such as exposure to viral infections (Leweke et al., 2004) autoimmune, toxic or traumatic insults and stress during gestation, birth or childhood (Marcelis et al., 1998 Cannon et al., 2000 Rosso et al., 2000) have been implied in the pathogenesis of schizophrenia. Lately, models based on epigenic factors and interaction between a susceptible genotype and the environmental factors have been proposed for this complex disease (Petronis, 2004). 

Environmental factors have been shown to be important triggers for expression of autoimmunity and have been suggested to both induce onset and modulate disease severity. Lifestyle factors such as diet, smoking, therapeutic and recreational drug use, infection with certain bacteria and viruses, and exposure to UV radiation and environmental chemicals have all been implicated in the pathogenesis of autoimmune diseases. 

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