Autoimmune response, elicitation

Some xenobiotics may have divergent mechanisms of autoimmune responses. For example, hydralazine demonstrates adduct reactivity as well as inhibition of DNA methylation [68,73], while procainamide inhibits DNA methylation, forms immunogenic NPA, and disrupts clonal selection in the thymus [68, 72, 74], It is this complicated pattern of effects that makes assessment of autoimmune potential in the laboratory for new xenobiotics almost impossible. Animal models can sometimes be recreated to resemble human disease [74], and thus may be useful for therapy considerations, but are difficult to utilize for screening chemicals for hazard potential due to the diverse nature of autoimmunity mechanisms and physiological presentation. While evidence supports many different mechanisms for xenobiotic-induced autoimmune reactions, none have conclusively demonstrated the critical events necessary to lead to the development of autoimmune disease. Therefore, it is difficult to predict or identify xenobiotics that might possess the potential to elicit autoimmune disorders. 

Individuals who are prone to develop autoimmune responses may be susceptible to the development of EMS due to implicated L-tryptophan. Many investigators who reviewed cases of EMS have suggested that an autoimmune mechanism was involved in EMS.50114-116 Some experimental studies with contaminants or impurities of implicated L-tryptophan have proposed mechanisms whereby abnormal proteins may be formed that may elicit an autoimmune response, with major consequences thereof.64 6598 Patients with EMS have increased levels of plasma neopterin, a marker of immune activation.58... 

Rheumatoid arthritis is an autoimmune disease. The antigen that stimulates the initial autoimmune response and the genetic mechanism that promotes its development are unknown. Once the disease process is under way, antigen-antibody complexes presumably activate the complement and elicit the release of various mediators, causing inflammation. The treatment of rheumatoid arthritis is aimed at reducing this inflammation, thereby decreasing the pain and attempting to slow the joint destruction. 

Autoimmune Diseases. PTM can dictate an antigen in eliciting autoimmune diseases. For example, isoaspartyl posttranslational modification (conversion of aspartic acid to isoaspartic acid) has been shown to trigger autoimmune response to self-proteins. The presence of isoaspartyl proteins has been observed as a major component of the amyloid containing brain plaques of patients with AD [46]. 

Biologies are sufficiently large and complex as to elicit immune responses directed to the protein. For the most part, the principal response elicited is a T cell-dependent humoral response. The development of an antibody response to a biologic in most cases has no adverse consequences (Schellekens 2002a Shankar et al. 2006). An antibody response is not an adverse event in itself. However, an antibody response to a biologic can have consequences that fall into three main categories hypersensitivity reactions, reduction in efficacy, and the induction of autoimmune disease (Schellekens 2002b). 

Cloning of genes that code for antigens capable of eliciting autoimmune response, vertebrate hormones, or exotoxins in bacteria capable of colonizing or infecting humans. 

This receptor is a member of the LDL receptor superfamily. It is the antigen that elicits an autoimmune response leading to a disease called Heymann s glomerulonephritis. It interacts with cubulin and is thought to function together with cubulin in the uptake of apo-Al by the kidney. 

Measuring muscle-evoked responses to repetitive motor nerve electrical stimulation permits detection of presyn-aptic neuromuscular junction dysfunction. In botulism and the Lambert-Eaton syndrome, repetitive stimulation elicits a smaller than normal skeletal muscle response at the beginning of the stimulus train, due to impaired initial release of acetylcholine-containing vesicles from presyn-aptic terminals of motor neurons followed by a normal or accentuated incremental muscle response during repeated stimulation. This incremental response to repetitive stimulation in presynaptic neuromuscular disorders can be distinguished from the decremental response that characterizes autoimmune myasthenia gravis, which affects the postsynaptic component of neuromuscular junctions. 

Strasser, A., S. Whittingham, D. L. Vaux, M. L. Bath, J. M. Adams, S. Cory, and A. W. Harris. 1991. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc. Natl. Acad. Sci. USA 88 8661-8665. 

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