Passive transfer of autoimmune disease with isologous IgG1 and IgG2 antibodies to the tubular basement membrane in strain XIII guinea pigs: loss of self-tolerance induced by autoantibodies

Abstract

Initiation of an autoimmune tubulointerstitial disease was achieved in strain XIII guinea pigs by passive transfer of functionally pure IgG1 or IgG2 fractions of isologous anti-tubular basement membrane (TBM) serum. IgG2 appeared to be somewhat more effective than IgG1. The immunopathologic features in the IgG1 and IgG2 recipients were similar at the time of sacrifice, 14 days after transfer. The recipients that developed disease had higher than expected anti-TBM titers at 14 days. Furthermore, anti-TBM antibodies were of both IgG isotypes. In contrast, simultaneously administered IgG1 or IgG2 anti-BGG antibodies declined in titer in the recipients and were never found in the isotype fraction that had not been transferred. These findings indicate that the recipients of anti-TBM antibodies of either IgG1 or IgG2 isotype were stimulated to produce anti-TBM autoantibodies, which participated in the pathogenesis of the renal disease. The model demonstrates that autoantibodies may provide a mechanism (autoimmune amplification) for the intensification and perpetuation of antibody-mediated autoimmune diseases.