Gold salts autoimmunity

Drugs can cause a wide variety of other autoimmune reactions. One example is myasthenia gravis, which is characterized by muscle weakness and is mediated by antibodies against the acetylcholine receptor at the neuromuscular junction. It has been reported in association with penicillamine [66], gold salts [67], and procainamide [68]. Another form of drug-induced autoimmunity is polymyositis, which is an autoimmune disease... 

Of all rat strains, the Brown Norway (BN) rat is used most frequently in relation to chemical-induced autoimmunity. This strain displays clinically manifested autoimmune disease following exposure to a number of chemicals. HgCl2 is the most scrutinized compound in the BN rat but D-penicillamine [6-8], gold-salts [9,10],hexachlorobenzene (HCB) [11-14] and recently, nevirapine [15], have all been shown to induce clinical effects. Captopril [7] and felbamate [16] appeared not to induce autoimmune effects in BN rats. 

Studies of xenobiotic-induced immune dysregulation in animal models. Hydralazine and procainamide-induced autoimmunity HgClj and gold salt-induced autoimmunity The impact of genetic studies in our understanding of immunological-mediated toxic-induced renal disease ... 

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. 

That gold salts possess immunosuppressive effects has been demonstrated by both in vivo and in vitro studies [56-59]. In addition, they also have an immu-noenhancing effect on the immune response of mice, depending on dosage [60]. BALB/c mice are highly susceptible to autoimmune interstitial nephritis, while C57BL/6 mice are genetically resistant to this nephritis... 

The exact phenotype of the regulatory T cells in the case of low-dose D-penicillamine tolerance is not known, and non-lymphoid cells probably play a role as well. In another example of drug-induced autoimmune responses, the phenotype of regulatory T cells was identified as CD4+CD25+ (Layland et ah, 2004). In this study, CD4+CD25+ cells isolated from mice (A/J strain) exposed to procainamide, mercuiy(II) chloride, or gold salts were capable of preventing antinuclear antibody formation in similarly treated recipient mice, but also in mice subsequently treated with one of the other two chemicals. 

Gold salts also induce an autoimmune syndrome in the Brown Norway rat similar to that observed with mercury(II) chloride (and... 

A number of studies have been performed to induce systemic immunosensitization and autoimmunity (i.e. autoantibody formation or autoreactive T cells) in mice, and, again, occurrence of disease appears to be strain dependent. Robinson et al. (1986) compared in one study a large number of MHC-defined mouse strains with respect to induction of antinuclear autoantibodies by mercury(II) chloride (subcutaneously, detected after 0.5-2 months), gold salts (intramuscularly, detected after 1-5 months), and D-penicillamine (orally, detected after 4.5-5 months) and reported that A.SW mice were high responders to all three chemicals. 

Hydralazine and procainamide-induced autoimmunity HgCI2 and gold salt induced autoimmunity... 

Saoudi A, Castedo M, Nochy D., Mandet C, Pasquier R, Druet P, Pelletier L. Self reactive anti-class II Th2 cell lines derived from gold salt-injected rats trigger B cell polyclonal activation and transfer autoimmunity in CD8-depleted normal syngeneic recipients. Eur J Immunol 1995 25 1972-1979. 

Gold" " salts injected subcutaneously over a 10-day period induced an autoimmune syndrome similar to that of HgCli in brown Norway rats. The auto-immune syndrome in both cases was characterized by a marked increase in IgE production, lymphoprolifera-tion, T cell-dependent polyclonal B cell activation, hypergammaglobulinaemia, and tissue injury widi necrotizing leucocytoclastic vasculitis in the gut at day 15 post-injection. 

---