GENETIC-STUDY OF GOLD-SALT-INDUCED IMMUNE DISORDERS IN THE RAT

Background. Rheumatoid arthritis patients treated with gold salts occa sionally develop a glomerulonephritis and an increase in serum IgE con centration. Brown-Norway (BN) rats injected with aurothiopropanolsulph onate (ATPS) exhibit an increase in serum IgE concentration, produce a ntilaminin antibodies (Abs) and develop glomerular linear immunoglobul in (Ig) deposits, occasionally a membranous glomerulopathy and vascula r granular Ig deposits. Lewis (LEW) rats are resistant. Methods. The g enetic requirements governing the appearance of these manifestations w ere studied in congenic rats, and in F1 hybrids injected with ATPS. Re sults. Non-MHC-linked genes from the BN strain were absolutely require d for all the traits to be observed. The RT1(n) (BN) or RT1(l) (LEW) h aplotypes at the MHC were permissive for all the manifestations to app ear and two RT1(l) alleles were associated with the highest response. However, granular Ig deposits were only observed in RTl(n) rats. The h igh serum IgE concentration and the antilaminin Ab level were associat ed with the presence of glomerular Ig deposits but were not associated with the presence of vascular Ig deposits. Conclusions. This study sh ows that susceptibility to ATPS was mainly dependent upon non-MHC-link ed BN genes and that the involvement of MHC-linked genes differed depe nding upon the character considered. There is an epistatic effect betw een the various genes.