Immunogenetically Controlled Autoimmune Reactions Induced by Mercury,Gold and D-Penicillamine in Laboratory Animals: a Review from the Vantage Point of Premarketing Safety Studies

Abstract

Mercury and gold salts as well as d-penicillamine can cause glome rulonephritis by an autoimmune mechanism in man. The suscepti bility to this effect of these chemicals is controlled by the genes of the major histocompatibility complex (MHC). The presence of cer tain 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 AS W mice were sensitive, several other strains were resist ant. 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.

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