Experimental gold-induced autoimmunity.
The pathogenesis of gold-induced autoimmunity and membranous glomerulopathy is not well understood. HgCl2 and D-penicillamine, other chemicals known to trigger membranous glomerulopathy in humans, induce autoimmune manifestations in Brown-Norway (BN) rats but not in Lewis (LEW) rats. These chemicals trigger T-cell clones which are specific for self class II molecules from the major histocompatibility complex and are probably responsible for the polyclonal B-cell activation observed. The aim of this work was to test the effects of aurothiopropanolsulphonate (ATPS) in BN and LEW rats. In BN rats, ATPS induced a polyclonal B-cell activation marked by lymphoproliferation, hyperimmunoglobulinaemia affecting mainly IgE, and by the production of numerous autoantibodies. A glomerulonephritis occurred, initially due to anti-glomerular basement membrane antibody deposition, and later to the formation of granular deposits, occasionally resulting in a typical membranous glomerulopathy. Self class-II-specific T-cells were found that might be responsible for the polyclonal B-cell activation. Lewis rats were free of glomerulopathy but, like BN rats, exhibited an interstitial nephritis and some degree of polyclonal B-cell activation. These findings demonstrate that, depending on the strain, ATPS triggers different B-cell clones inducing different degrees of autoimmunity.
Tournade
H
H
INSERM U28, Hôpital Broussais, Paris, France.
Guery
J C
JC
Pasquier
R
R
Nochy
D
D
Hinglais
N
N
Guilbert
B
B
Druet
P
P
Pelletier
L
L
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity / Q000187:drug effects*; D004112:Dimercaprol / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D006046:Gold / Q000633:toxicity*; D007073:Immunoglobulin E / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D050607:Organogold Compounds; D009942:Organometallic Compounds / Q000633:toxicity*; D020005:Propanols; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D013438:Sulfhydryl Compounds
D001323:Autoantibodies; D050607:Organogold Compounds; D009942:Organometallic Compounds; D020005:Propanols; D013438:Sulfhydryl Compounds; D004112:Dimercaprol; D007073:Immunoglobulin E; D006046:Gold; C013394:aurotioprol