Immunogenetically controlled autoimmune reactions induced by mercury, gold and D-penicillamine in laboratory animals: a review from the vantage point of premarketing safety studies.

Mercury and gold salts as well as d-penicillamine can cause glomerulonephritis by an autoimmune mechanism in man. The susceptibility to this effect of these chemicals is controlled by the genes of the major histocompatibility complex (MHC). The presence of certain alleles confers sensitivity. The role of MHC-linked genes has been demonstrated also in the rat and mouse in the development of autoimmunity induced by these chemicals. While Brown Norway rats and ASW mice were sensitive, several other strains were resistant. Also an interaction of MHC with background genes has been shown in determination of the response to HgCl2. In conventional toxicity studies, use of a single inbred strain of laboratory animals obviously handicaps the detection of a reaction of this nature.