Genetic study of gold-salt-induced immune disorders in the rat.
BACKGROUND
Rheumatoid arthritis patients treated with gold salts occasionally develop a glomerulonephritis and an increase in serum IgE concentration. Brown-Norway (BN) rats injected with aurothiopropanolsulphonate (ATPS) exhibit an increase in serum IgE concentration, produce antilaminin antibodies (Abs) and develop glomerular linear immunoglobulin (Ig) deposits, occasionally a membranous glomerulopathy 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 RT1(1) (LEW) haplotypes at the MHC were permissive for all the manifestations to appear and two RT1(1) 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.
Kermarrec
N
N
INSERM U28, Hôpital Broussais, Paris, France.
Blanpied
C
C
Pelletier
L
L
Feingold
N
N
Mandet
C
C
Druet
P
P
Hirsch
F
F
D000704:Analysis of Variance; D000818:Animals; D018501:Antirheumatic Agents / Q000633:toxicity*; D004112:Dimercaprol / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000097:blood / Q000139:chemically induced / Q000235:genetics*; D007073:Immunoglobulin E / Q000097:blood*; D008297:Male; D050607:Organogold Compounds; D009942:Organometallic Compounds / Q000633:toxicity*; D010641:Phenotype; D020005:Propanols; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013438:Sulfhydryl Compounds
D018501:Antirheumatic Agents; D050607:Organogold Compounds; D009942:Organometallic Compounds; D020005:Propanols; D013438:Sulfhydryl Compounds; D004112:Dimercaprol; D007073:Immunoglobulin E; C013394:aurotioprol