Autoimmunity metals

Penicillamine onset may be seen in 1 to 3 months, and most responses occur within 6 months. Early adverse effects include skin rash, metallic taste, hypogeusia, stomatitis, anorexia, nausea, vomiting, and dyspepsia. Glomerulonephritis may occur, which manifests as proteinuria and hematuria. Penicillamine is usually reserved for patients who are resistant to other therapies because of the rare but potentially serious induction of autoimmune diseases (e.g., Goodpasture s syndrome, myasthenia gravis). 

Rowley, B. and Monestier, M. Mechanisms of heavy metal-induced autoimmunity, Mol. Immunol., 42, 833, 2005. 

Druet, P. et al., Autoimmune reactions induced by metals, in Autoimmunity and Toxicology Immune Dysregulation Induced by Drugs and Chemicals, Kammunller, M.E., Blocksma, N., and Seinen, W., Eds., Elsevier, Amsterdam, 1989, 347. 

Monestier, M., Novick, K.E., and Losman, M.J., D-penicillamine- and quinidine-induced antinuclear antibodies in A.SW (H-2s) mice Similarities with autoantibodies in spontaneous and heavy metal-induced autoimmunity. Eur. J. Immunol., 24, 723, 1994. 

Immunological Injury. Defects in immunological function may be manifested by such conditions as recurrent infection, autoimmune disease, and lymphoma (129). It is hypothesized that heavy metals may alter the function of sulfur-rich immunoproteins by displacing trace element cofactors (96). Lead burdens in mice, rats, and baboons similar to those... 

Heavy metals, like lead and mercury, have been recognized as toxic poisons for centuries. Further, toxic concentrations of mercury, for example, can trigger several effects like autoimmune diseases, infections, unexplained chronic fatigue, depression, nerve impairment, memory problems, decreased mental clarity, and bowel disorders. For several decades, mercury vapor exposure has caused severe health problems among chloralkali workers. This is only an example. It may be repeated that education can effectively minimize exposure to hazardous metals. Basic information and training for proper handling of toxic chemicals will reduce potential adverse health effects. 

Bigazzi PE. Metals and kidney autoimmunity. Environ Health Perspect 1999 107(Suppl 5) 753-65. 

Immunological-mediated toxic-induced renal diseases are multifactorial Genetic control of metal-induced autoimmunity and nephropathy... 

Figure 3. Effects of heavy metals (Hg andAu) on Immune cells. Hg was described as able to interact with the nuclear antigen fibrillarin which was assumed to cause a T-cell response against this modified autoantigen. True autoreactive T-ceiis specific for the native antigen were detected in a second time. Hg was shown to induce the expression of a normally cryptic epitope of RNAse A leading to the activation of specific T-cells. However the relevance of this mechanism in terms of induction of autoimmunity has not been demonstrated. Hg orAu have also been shown to poiyctonaity activate T-cells mimicking the effects of stimulation with anti-TCR antibodies. This results in an increase in intracellular Ca concentration, MAP kinase activation and cytokine expression.

The fact that normal BN T-cells incubated with HgCl2 transferred the disease [131] suggested that the effect of the metal on T-cells was sufficient for the induction of autoimmunity. Figure 3 summarizes some events by which HgCl2 or gold salts may induce autoreactivity. 

Genetic control of metal-induced autoimmunity and nephropathy... 

An experimental model of metal-induced autoimmunity and nephropathy has been developed in the BN rat, which is genetically predisposed to develop Th2-type of immune response. In the BN rat, the injections of... 

These differences between BN and LEW rats in susceptibility to metal-induced autoimmunity and nephropathy are associated with intrinsic differences in the immune system of these two strains. Indeed, from an immunological point of view, the balance between "type 1" (Thl/Tcl) and "type 2" (Th2/Tc2) cells is opposite in BN and LEW rats. BN rats are susceptible to "type 2"-mediated immunological disorders, to which the LEW strain is resistant. Conversely, "type l"-mediated organ-specific autoimmune disease are easily induced in LEW, but not in BN rats [155]. These immunological features depend on inherent properties of T lymphocytes. In vitro and in vivo studies have shown an inherent bias in T lymphocytes (CD4 and CDS) from BN and from LEW rats to produce respectively "type 2" (IL-4, IL-5, IL-13) and "type 1" (IFN-y cytokines [156-158]. The difference in susceptibility to metal-induced autoimmunity and nephropathy of BN and LEW strains provides a unique tool to study their genetic control. 

Griem P, Gleichmann E Metal ion-induced autoimmunity. Curr. Opin. Immunol. 1995 7 831-838. 

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