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Nephrol Dial Transplant (1995) 10: 2187-2191
© 1995 European Renal Association-European Dialysis and Transplant Association

research-article

Genetic study of gold-salt-induced immune disorders in the rat

N. Kermarrec1, C. Blanpied1, L. Pelletier1, N. Feingold2, C. Mandet1, P. Druet1 and F. Hirsch1,

1INSERM U28, H{circumflex}pital Broussais, Universite Paris VI Paris, France 2INSERM U155, Universite Paris VI Paris, France

Correspondence and offprint requests to: Correspondence and offprint requests to: Dr Hirsch Francois, CNRS UPR420, 19 rue Guy Moquet, 94801 Villejuif cedex, France

BACKGROUND: Rheumatoid arthritis patients treated with gold salts occasionally develop a glomerulo-nephritis and an increase in serum IgE concentration. Brown-Norway (BN) rats injected with aurothiopro-panolsulphonate (ATPS) exhibit an increase in serum IgE concentration, produce antilaminin antibodies (Abs) and develop glomerular linear immunoglobulin (Ig) deposits, occasionally a membranous glomerulo-pathy and vascular granular Ig deposits. Lewis (LEW) rats are resistant.

METHODS: The genetic requirements governing the appearance of these manifestations were studied in congenic rats, and in F1 hybrids injected with ATPS.

RESULTS: Non-MHC-linked genes from the BN strain were absolutely required for all the traits to be observed. The RT1n (BN) or RT11 (LEW) haplotypes at the MHC were permissive for all the manifestations to appear and two RT11 alleles were associated with the highest response. However, granular Ig deposits were only observed in RT1n rats. The high serum IgE concentration and the antilaminin Ab level were associated with the presence of glomerular Ig deposits but were not associated with the presence of vascular Ig deposits.

CONCLUSIONS: This study shows that susceptibility to ATPS was mainly dependent upon non-MHC-linked BN genes and that the involvement of MHC-linked genes differed depending upon the character considered. There is an epistatic effect between the various genes.

Keywords: gold salts; autoimmunity; genetic; rat


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