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.

Cerebral lupus erythematosus responding to plasmaphaeresis

“…In the short term there is presumably a reduction of the agent(s), antineuronal antibodies or immune complexes, which determine the pathogenesis of cerebral lupus. The long-term benefit, exemplified by the present case, may be attributable to abrogation of the process of autoimmune amplification described by Hall et al (1977). Finally this case suggests that shorter than conventional courses of plasma exchange may be effective in ameliorating the course of SLE.…”

Studies on the Pathogenesis of Experimental Autoimmune Renal Tubulointerstitial Disease in Guinea Pigs

“…Several hy potheses can be offered for this variation in degree of inflammatory response, e.g., dif ferences in the amount of antibody fixed by the TBM of the two strains or defects in effector systems or in inflammatory cells. Autoimmune amplification [3] as noted in strain 13 passive transfer recipients may also play a role although our studies in the radiation chimeras argue against this possi bility. It is also possible that the Albany an ti-TBM serum contained antibodies to more strain 2 TBM determinants than did Hartley donor serum.…”

“…Previous reports [4,5] indicated that strain 2 guinea pigs do not develop RTD and that they differ significantly in their im mune and inflammatory responses from strain 13 [3,4,6], Hartley [4,6,14,17], C4-deficicnt [8], NIH multipurpose [8], and Albany [14] guinea pigs. Three major dif ferences were alleged: active immunization of strain 2 with TBM was ineffective in in ducing autoantibodies unless large amounts of antigen were injected [4|.…”

Circulating Anti-Tubular Basement Membrane Antibody in a Variety of Human Renal Diseases

“…A second factor described experimentally is the difference in susceptibility of certain strains to develop the lesions of interstitial nephritis even after anti-TBM antibody formation. These authors indi cate that a certain genetic background is necessary before full expression of the disease is seen [12][13][14], Close exam ination of published papers suggests this same variation in end organ response is seen in humans. Maliieu ei al.…”