SELECTIVE INDUCTION OF ANTI-FIBRILLARIN AUTOANTIBODIES BY SILVER-NITRATE IN MICE

Female SJL (H-2(S)) mice developed serum IgG anti-nucleolar antibodies (ANoA) after 5 weeks treatment with 0.05% or 0.01% silver nitrate (Ag NO3) in drinking water. Five more weeks of treatment increased the ANo A titre to 3410+/-853 and 640+/-175 (reciprocal mean+/-s.e.m.), respec tively. Controls receiving ordinary tap water and mice given 0.002% Ag NO3 showed no antinucleolar antibodies. The high-titre ANoA targeted a 34-kD nucleolar protein identified as fibrillarin, the major autoanti gen in murine mercury-induced autoimmunity and in a fraction of patien ts with systemic scleroderma. Serum autoantibodies to chromatin or his tones, kidney, spleen, stomach, thyroid, or skin antigens (except the nucleolus) were not found in any of the mice. There was no consistent significant increase of serum IgG1, IgG2a, IgG2b, or IgC3 concentratio ns after AgNO3 treatment compared with controls. Mice treated with 0.0 5% AgNO3 for 10 weeks showed a slight decrease in serum IgG1, IgG2b an d IgG3 concentrations. These mice also showed a small but statisticall y significant increase in renal, mesangial IgM deposits, which was not accompanied by any increase in C3c deposits, whereas mice given lower doses of silver nitrate showed no significant increase in mesangial i mmunoglobulin immune deposits. Systemic vessel wall immune deposits we re not found in any of the mice. In mice given 0.05% silver nitrate, t he kidney showed the highest concentration of silver (12.2+/-0.09 mu g Ag/g wet weight; mean+/-s.e.m), followed by the spleen (8.7+/-1.3), a nd the liver (3.9+/-0.4). Treatment with 0.01% silver nitrate caused a different distribution of silver, with the highest concentration in t he spleen (2.1+/-0.16 mu g Ag/g), followed by the kidney (0.63+/-0.037 ), and the liver (<0.29 mu g Ag/g; mean). Silver seems to be a more sp ecific inducer of anti-nucleolar/anti-fibrillarin autoantibodies than mercury and gold, lacks the general immune stimulating potential of me rcury, and has only a weak tendency to induce renal immune deposits. T hese observations suggest that the autoimmune sequelae induced in mice by metals is dependent, not only upon the genetic haplotype of the mu rine strain, but also on the metal under investigation.