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.

References

Balazs, T. , Robinson, C.J.G. and Abraham, A. (1986). Drug-induced autoimmunity in rats. Abstract 5:432, 6th International Congress on Immunology, Toronto.

Batchelor, J.R. , Welsh, K.I. , Tinoco, R.M. , Dollery, C.T. , Hughes, G.R.V. , Bernstein, R. , Ryan, P. , Naish, P.F. , Aber, G.M. , Bing, R.F. and Russell, G.I. (1980). Hydralazine-induced systemic lupus erythematosus: Influence of HLA-DR and sex on susceptibility. Lancet 1:1107-1109.

Donker, A.J. , Venuto, R.C. , Vladutiu, A.O. , Brentjens, J.R. and Andres, G.A. (1984). Effects of prolonged administration of D-penicillamine or captopril in various strains of rats. Clin. Immunol. Immunopathol . 30:142-155.

Druet, P. , Baran, D. , Pelletier, L. , Hirsch, F. , Druet, E. and Sapin, C. (1986). Drug-induced experimental autoimmune nephritis . Concepts Immunopathol. 3:311-330.

Hill, G.S. (1986). Drug associated glomerulopathies. Toxicol. Pathol. 14:37-44.

Malinow, M.R. , Bardana, E.J. , JR., Pirofsky, B. , Craig, S. and Maclaugh-Lin, P. (1982). Systemic lupus erythematosus-like syndrome in monkeys fed alfalfa sprouts: Role of a nonprotein amino acid . Science 216:415-417.

Pereyo, N. (1980). Tartrazine and drug-induced lupus. Schock Lett. 30:1.

Reidenberg, M.M. , Durant, P.J. , Harris, R.A. , Deboccardo, G. , Lahita, R. and Stenzel, K.H. (1983). Lupus erythematosus-like disease due to hydrazine . Am. J. Med. 75:365-370.

Robinson, C.J.G. , Balazs, T. and Egorov, I.K. (1986). Mercuric chloride-, gold sodium thiomalate-, and D-penicillamine-induced antinuclear antibodies in mice. Toxicol. Appl. Pharmacol. 86:159-169.

10.

Vicario, J.L. , Serrano-Rios, M. , San Andres, F. and Arnaiz-Villena, A. (1982). HLA-DR3, DR4 increase in chronic stage of Spanish oil disease. Lancet 1:276.

11.

Weening, J.J. , Fleuren, G.J. and Hoedemaeker, P.J. (1978). Demonstration of antinuclear antibodies in mercuric chloride-induced glomerulopathy in the rat. Lab. Invest. 39:405-411.