Interaction of xenogeneic antiglomerular antibodies with foetal pig tissues.
Rabbit anti-swine-glomerular-immunoglobulin (AG Ig) was administered in utero to 14 pig foetuses 40-103 d post-conception. In nine foetuses AG Ig was injected into the umbilical vein and 60 min later kidneys and other organs were collected. In five others, AG Ig was injected via the intact uterine wall, and the tissues were examined after further 11 or 35 d of uninterrupted pregnancy. No signs of glomerular inflammation were found by light microscopy. In electron microscopy, especially in younger foetuses, focal endothelial defects and subendothelial granular "deposits" were seen in deep glomeruli, but they appeared also in control foetuses of corresponding age. Immunofluorescence microscopy showed a strong diffuse linear positivity of the swine-anti-rabbit-Ig conjugate in the capillary loops of deep juxtamedullary glomeruli irrespective of foetal age and dose of antigen injected. Immature glomeruli and S-bodies yielded a poor to negative staining. Proof of swine Ig was negative in all kidneys as well as the test for rabbit and swine Ig in various other organs. Traces of rabbit Ig were only detected in disseminated platelet aggregates of myocardium in the early post-injection period. Ultrastructural enzyme-antibody assay visualized AG Ig throughout all three layers of glomerular capillary basement membrane, and in the early period signs of transendothelial passage and escape of unbound rabbit Ig molecules were evident. The mesangial matrix, cell membranes, and extraglomerular basement membranes remained all negative. As follows, xenogeneic antiglomerular antibodies specifically react with target structures even at the end of the first third of intrauterine life, afflicted being only the deep mature polyanion-coated glomeruli. The foetal immune system is incapable of an adequate autologous antibody response, and we have failed to find even an early glomerular lesion comparable with the postnatal anti-basement-membrane glomerulonephritis.