Experiments will be performed on experimental glomerulonephritides, poststreptococcal nephritis, nephritis produced by mercuric chloride and by cationized IgG. Also, definite information about the mechanism of immune complex glomerulonephritis in chronic graft-versus-host reaction will be sought in experiments involving renal allografts in mice. The hyperacute rejection of renal grafts, which was shown to be elicited by humoral antibodies to transplantation antigens, has been avoided by cross-matching procedures. This, however, excludes hundreds of potential recipients from the benefits of renal grafts. Studies are proposed on means to achieve acceptance of a renal allograft in spite of a positive cross-match. The previously developed in vitro model for organ rejection involving perfusion of heart with antibody-containing sera will be used for these studies along with in vivo kidney graft in rabbits presensitized by skin grafts. The agents counteracting pharmacological mediators of hyperacute rejection will be studied as well as the effect of depriving the sensitized animal of antibodies and complement by plasmapheresis. Xenografts become a necessity in clinical transplantation because of the paucity of human organs available for transplantation. Approaches explored to avoid hyperacute rejection of xenografts will be similar to those studied in relation to allografts. Donor- sepcific unresponsivenes to renal allografts will be studied in mice and in man to identify humoral antibodies which participate in this unresponsiveness and whch possibly could be applied in human transplantation. Late deterioration of renal allografts which survived the rejection but which are exposed to a de novo immunological disorder will be studied in continuation of studied conducted in previous years of glomerular and tubular lesions in the grafts. Serological parameters or renal grafrt rejection will be explored with the final objective of developing serodiagnostic tests for predicting and recognizing rejection. This study will be primarily preoccupied with detection of IgG rheumatoid factor, but also studies will be continued on heterophile transplantation antibodies and antibodies to Wassermann-like antigens. Furthermore, antibodies to antigens shed off from the graft undergoing rejection will be detected as well as attempts will be made to demonstate such antigens in the patient's serum and urine.
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